Study Reveals Gophers’ Biofluorescence

You can learn a lot about animals by simply watching them. But some secrets can only be revealed in the dark … with an ultraviolet flashlight. This happens to be the case for pocket gophers, small rodents that live underground in sandy soil. A new paper by University of Georgia (UGA) researchers found that these feisty, solitary, round-cheeked animals have a special capability that’s only revealed under ultraviolet light: They are biofluorescent, giving off a colored glow when illuminated with UV light. Image shows pocket gopher illuminated with UV light (Credit: UGA). Published online on July 19, 2021 in The American Midland Naturalist,  this is the first time biofluorescence has been documented in pocket gophers. J.T. Pynne, a recent PhD graduate of the UGA Warnell School of Forestry and Natural Resources and lead author of the study, said he was inspired to shine a light on the possibility a few years ago, after reading similar studies documenting the phenomenon in flying squirrels and opossums. The new article is titled “Ultraviolet Biofluorescence in Pocket Gophers.”

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Mutated Tumor Suppressor Genes Interfere with Adaptive Immune System Attack on Tumor Cells; New Results Reveal “Fascinating and Unexpected Relationship Between Tumor Suppressor Genes and the Immune System,” Says HHMI Investigator Bert Vogelstein in Comment on Harvard/HHMI-Led Study Published in Science

Hundreds of cancer-linked genes play a different role in causing disease than scientists had expected. So-called tumor suppressor genes have long been known to block cell growth, preventing cancerous cells from spreading. Mutations in these genes, scientists believed, thus allow tumors to flourish unchecked. Now, Howard Hughes Medical Institute (HHMI) Investigator and Gregor Mendel Professor of Genetics and of Medicine at Harvard Medical School Stephen Elledge (photo), PhD, and his team have uncovered a surprising new action for many of these defective genes. More than 100 mutated tumor suppressor genes can prevent the immune system from spotting and destroying malignant cells in mice, according to Dr. Elledge, also a geneticist at Brigham and Women’s Hospital, and colleagues, who reported their results online on September 17, 2021, in Science. “The shock was that these genes are all about getting around the immune system, as opposed to simply saying ‘grow, grow, grow!’” Dr. Elledge says. The Science article is titled “The Adaptive Immune System Is a Major Driver of Selection for Tumor Suppressor Gene Inactivation.” 

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Takeda’s EXKIVITY™ (Mobocertinib) Approved by U.S. FDA As First Oral Therapy Specifically Designed for Patients with EGFR Exon20 Insertion-Positive Non-Small Cell Lung Cancer (NSCLC); Next-Generation Sequencing (NGS) Companion Diagnostic from Thermo Fisher Scientific Approved Simultaneously

On September 15, 2021, Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) announced that the U.S. Food and Drug Administration (FDA) has approved EXKIVITY (mobocertinib) for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. EXKIVITY, which was granted priority review and received Breakthrough Therapy Designation, Fast Track Designation, and Orphan Drug Designation from the FDA, is the first and only approved oral therapy specifically designed to target EGFR Exon20 insertion mutations. This indication is approved under Accelerated Approval based on overall response rate (ORR) and durability of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

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FDA Approves Tissue-Based Next-Generation Sequencing (NGS) Companion Diagnostic (CDx) for Takeda’s Targeted Therapy (EXKIVITY) for Non-Small Cell Lung Cancer (NSCLC) Patients with EGFR Exon20 Insertion Mutations; Thermo Fisher Scientific’s Oncomine Dx Target Test Now Approved As CDx for Five Targeted NSCLC Therapies in U.S.

On September 15, 2021, Thermo Fisher Scientific announced that the U.S. Food and Drug Administration (FDA) has granted pre-market approval to Thermo Fisher Scientific’s Oncomine Dx Target Test as a companion diagnostic (CDx) to identify patients with epidermal growth factor receptor (EGFR) Exon20 insertion mutation-positive metastatic non-small cell lung cancer (mNSCLC) who are candidates for EXKIVITY™ (mobocertinib), a targeted drug developed by Takeda Pharmaceutical Company Limited. EXKIVITY is a small-molecule tyrosine kinase inhibitor (TKI) designed to selectively target EGFR Exon20 insertion mutations. It received approval by the FDA on September 15, 2021 for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (mNSCLC) with EGFR Exon20 insertion mutations as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. This indication is approved under Accelerated Approval based on overall response rate and duration of response demonstrated in the platinum-pretreated population of the Phase 1/2 trial of EXKIVITY. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

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Protein from Liver May Cause Alzheimer’s Disease (AD) in the Brain; Peripherally Produced Amyloid Causes Neurodegeneration; Results Suggest Dietary Approach and/or Targeted Drugs May Be Helpful in Preventing/Treating AD

Amyloid protein made in the liver can cause neurodegeneration in the brain, according to a new study in the open-access journal PLOS Biology, by lead investigator John Mamo, PhD, of Curtin University in Bentley, Australia, and colleagues. Because the protein is thought to be a key contributor to development of Alzheimer’s disease (AD), the results suggest that the liver may play an important role in the onset or progression of the disease. The open-access article was published online on September 14, 2021 and is titled “Synthesis of Human Amyloid Restricted to Liver Results in an Alzheimer Disease–Like Neurodegenerative Phenotype.”

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Researchers in Japan Use New Supercomputer Analysis to Predict and Confirm a Key Protein (HMGB1) Mediator of Dementia in Frontotemporal Lobar Degeneration (FTLD) and Alzheimer Disease; Treatment with Anti-HMGB1 Antibody Shows Promise

Dementia has many faces, and because of the wide range of ways in which it can develop and affect patients, it can be very challenging to treat. Now, however, using supercomputer analysis of big data, researchers from Japan have been able to predict that a single protein is a key factor in the damage caused by two very common forms of dementia. In a study published online on August 12, 2021 in Communications Biology, researchers from Tokyo Medical and Dental University (TMDU) have revealed that the protein HMGB1 (high mobility group box 1) is a key player in both frontotemporal lobar degeneration (FTLD) and Alzheimer disease, two of the most common causes of dementia. The open-access article is titled “Prediction and Verification of the AD-FTLD Common Pathomechanism Based on Dynamic Molecular Network Analysis.”

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Engineers Grow Pancreatic “Organoids” That Mimic Real Pancreas; Studying These Organoids Could Help Researchers Develop and Test New Treatments for Pancreatic Cancer; Development of Specialized Growth Gel by MIT Scientists Is Key to Advance

MIT engineers, in collaboration with scientists at the Cancer Research UK Manchester Institute, have developed a new way to grow tiny replicas of the pancreas, using either healthy or cancerous pancreatic cells. Their new models could help researchers develop and test potential drugs for pancreatic cancer, which is currently one of the most difficult types of cancer to treat. Using a specialized gel that mimics the extracellular environment surrounding the pancreas, the researchers were able to grow pancreatic “organoids,” allowing them to study the important interactions between pancreatic tumors and their environment. Unlike some of the gels now used to grow tissue, the new MIT gel is completely synthetic, easy to assemble, and can be produced with a consistent composition every time.

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Plant Virus Could Protect and Save Lungs from Metastatic Cancer

Using a virus that grows in black-eyed pea plants, nanoengineers at the University of California San Diego (UCSD) have developed a new treatment that could keep metastatic cancers at bay from the lungs. The treatment not only slowed tumor growth in the lungs of mice with either metastatic breast cancer or melanoma, it also prevented or drastically minimized the spread of these cancers to the lungs of healthy mice that were challenged with the disease. The research was published online on September 14, 2021 in Advanced Science. The open-access article is titled “S100A9-Targeted Cowpea Mosaic Virus as a Prophylactic and Therapeutic Immunotherapy against Metastatic Breast Cancer and Melanoma.” Cancer spread to the lungs is one of the most common forms of metastasis in various cancers. Once there, it is extremely deadly and difficult to treat. Researchers at the UCSD Jacobs School of Engineering developed an experimental treatment that combats this spread. It involves a bodily injection of a plant virus called the cowpea mosaic virus (image). The virus is harmless to animals and humans, but it still registers as a foreign invader, thus triggering an immune response that could make the body more effective at fighting cancer.

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Programming Synthetic Exosomes to Optimize Wound Healing & Formation of New Blood Vessels: Scientists Create Synthetic Exosomes with Natural Functionalities and Present Their Therapeutic Application

Scientists from the Max Planck Institute for Medical Research in Heidelberg, Germany, and colleagues at the DWI Leibniz Institute for Interactive Materials in Aachen, Germany, have engineered synthetic exosomes that regulate cellular signaling during wound closure. The synthetic structures are built to resemble naturally occurring extracellular vesicles (EVs) [Editor’s Note: Exosomes are a subset of EVs] that play a fundamental role in communication between cells during various processes in our body. The scientist uncovered key mechanisms to regulate and aid wound healing and the formation of new blood vessels. For this, they designed and built programmable fully-synthetic EVs from scratch rather than isolating natural EVs from cells. Inspired by the function of their natural blue prints, the scientists successfully demonstrate for the first time that fully-synthetic exosomes with therapeutic functionality can be constructed. The new work was reported online on September 3, 2021 in Science Advances. The open-access article is titled “Bottom-Up Assembly of Biomedical Relevant Fully Synthetic Extracellular Vesicles.”

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Comparison of T Cells from HIV “Controllers” (HIV-Infected Patients Who Control Infection Without Medication) with T Cells from “Aborted Controllers” (Who Ultimately Lose Control and Must Be Medicated) Reveals Early T Cell Dysfunction Different from Canonical T Cell Dysfunction Seen in Vast Majority of HIV Patients

HIV is a master of evading the immune system, using a variety of methods to prevent the body from being able to find and kill it. The vast majority of people living with HIV require daily medication to suppress the virus and therefore prevent the development of AIDS. But, for a small subset of people, this battle between the immune system and the virus looks quite different. Known as “controllers,” these patients have immune systems that can suppress the virus without any need for medication. Whereas most controllers can suppress the virus indefinitely, some eventually lose control over the virus and require medication to achieve viral suppression. In a paper published online on September 7, 2021 in Immunity,  Harvard Medical School (HMS) researchers at the Ragon Institute of MGH, MIT, and Harvard reported that, in these cases, control is lost after a type of immune cell, called a cytotoxic T cell, loses the ability to proliferate and kill HIV-infected cells. 

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