Artificial Intelligence Can Reliably Diagnosis Specific Types of Lung Cancer

MedicalResearch.com Interview with:

Aristotelis Tsirigos, Ph.D. Associate Professor of Pathology Director, Applied Bioinformatics Laboratories New York University School of Medicine

Dr. Tsirigos

Aristotelis Tsirigos, Ph.D.
Associate Professor of Pathology
Director, Applied Bioinformatics Laboratories
New York University School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Pathologists routinely examine slides made from tumor samples to diagnose cancer types. We studied whether an AI algorithm can achieve the same task with high accuracy. Indeed, we show that such an algorithm can achieve an accuracy of ~97%, slightly better than individual pathologists.

In addition, we demonstrated that AI can be used to predict genes that are mutated in these tumors, a task that pathologists cannot do. Although the accuracy for some genes is as high as 86%, there is still room for improvement. This will come from collecting more training data and also from improvement in the annotations of the slides by expert pathologists.  

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IMPRES Score Predicts Melanoma Response to Immunotherapy

MedicalResearch.com Interview with:

Melanoma CDC/ Carl Washington, M.D., Emory Univ. School of Medicine; Mona Saraiya, MD, MPH

This image depicts the gross appearance of a cutaneous pigmented lesion, which had been diagnosed as superficial spreading malignant melanoma (SSMM).  Reminder: Melanoma can take many forms. Not all look like this. Have your skin examined for skin cancer.

Dr. Noam Auslander PhD
National Cancer institute and the Center for Bioinformatics and Computational Biology University of Maryland, College Park

MedicalResearch.com: What is the background for this study?

Response: Immunotherapy – specifically immune checkpoint blockage (ICB) therapy – has been shown to be very effective in treating melanoma. However, only some patients with advanced tumors currently benefit from ICB therapies, while others are completely resistant and hence can be spared from the associated side effects and costs. Hence, predicting which patients are most likely to respond is an important challenge that can have great clinical benefits.   Continue reading

 Four Brain-Guided Dimensions of Psychopathology: Mood, Psychosis, Fear, and Disruptive Behavior

MedicalResearch.com Interview with:
MedicalResearch.com Interview with: Dr. Theodore Satterthwaite MD Assistant professor in the department of Psychiatry, and Cedric Xia, a MD-PhD candidate Perelman School of Medicine at the University of Pennsylvania MedicalResearch.com: What is the background for this study? What are the main findings? Response: Unlike other branches of modern medicine, psychiatry still solely replies on patient reports and physician observations for clinical decision-making. Without biologically-based tests, the diagnostic categories for mental health do not carve nature at its joint. This is evident in the high levels of co-morbidity across disorders and heterogeneity within disorders. Through this research, we studied a large sample of adolescents who completed MRI-based functional imaging, and used recently-developed machine learning techniques to uncover specific abnormalities that are highly predictive of a wide variety of psychiatric symptoms. Essentially, we tried to find brain patterns that were predictive of different types of psychiatric symptoms. We discovered four such brain-guided dimensions of psychopathology: mood, psychosis, fear, and disruptive behavior. While each of these dimensions exhibits a unique pattern of brain connectivity, a common feature of brain anomaly is shared across the dimensions. Notably, in all linked dimensions, the default mode network and fronto-parietal network, two brain regions that usually become increasingly distinct as the brain matures, were abnormally connected. This loss of normal brain network segregation supports the hypothesis that many psychiatric illnesses may be disorders of brain development. MedicalResearch.com: What should readers take away from your report? Response: This study shows that we can start to use the brain to guide our understanding of psychiatric disorders in a way that’s fundamentally different than grouping symptoms into clinical diagnostic categories. By moving away from clinical labels developed decades ago, we can begin to let the biology speak for itself. Our ultimate hope is that understanding the biology of mental illnesses will allow us to develop better treatments for our patients. MedicalResearch.com: What recommendations do you have for future research as a result of this work? Response: This study demonstrates the importance of incorporating vast amounts of biological data to study mental illness across clinical diagnostic boundaries. Moving forward, we hope to integrate genomic data in order to describe pathways from genes to brain to symptoms, which could ultimately be the basis for novel treatments for mental illness. MedicalResearch.com: Is there anything else you would like to add? Response: Future breakthroughs in brain science to understand mental illness requires large amount of data. While the current study takes advantage of one of the largest samples of youth, the size (n=999) remains dwarfed by the complexity of the brain. The neuroscience community is actively working towards collecting higher quality data in even larger samples, so we can validate and build upon the findings. Citation: Cedric Huchuan Xia, Zongming Ma, Rastko Ciric, Shi Gu, Richard F. Betzel, Antonia N. Kaczkurkin, Monica E. Calkins, Philip A. Cook, Angel García de la Garza, Simon N. Vandekar, Zaixu Cui, Tyler M. Moore, David R. Roalf, Kosha Ruparel, Daniel H. Wolf, Christos Davatzikos, Ruben C. Gur, Raquel E. Gur, Russell T. Shinohara, Danielle S. Bassett, Theodore D. Satterthwaite. Linked dimensions of psychopathology and connectivity in functional brain networks. Nature Communications, 2018; 9 (1) DOI: 10.1038/s41467-018-05317-y  <span class="last-modified-timestamp">Aug 8, 2018 @ 1:10 am</span> The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.
Dr. Theodore Satterthwaite MD
Assistant professor in the department of Psychiatry, and
Cedric Xia, a MD-PhD candidate
Perelman School of Medicine at the University of Pennsylvania

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Unlike other branches of modern medicine, psychiatry still solely replies on patient reports and physician observations for clinical decision-making. Without biologically-based tests, the diagnostic categories for mental health do not carve nature at its joint. This is evident in the high levels of co-morbidity across disorders and heterogeneity within disorders.

Through this research, we studied a large sample of adolescents who completed MRI-based functional imaging, and used recently-developed machine learning techniques to uncover specific abnormalities that are highly predictive of a wide variety of psychiatric symptoms. Essentially, we tried to find brain patterns that were predictive of different types of psychiatric symptoms. We discovered four such brain-guided dimensions of psychopathology: mood, psychosis, fear, and disruptive behavior.

While each of these dimensions exhibits a unique pattern of brain connectivity, a common feature of brain anomaly is shared across the dimensions. Notably, in all linked dimensions, the default mode network and fronto-parietal network, two brain regions that usually become increasingly distinct as the brain matures, were abnormally connected. This loss of normal brain network segregation supports the hypothesis that many psychiatric illnesses may be disorders of brain development. Continue reading

Yin Yang 1 Regulatory Protein May Help Breast Cancer Evade Treatment

MedicalResearch.com Interview with:

Luca Magnani, Ph.D CRUK Fellow/Senior Research Fellow Department of Surgery and Cancer Imperial Centre for Translational and Experimental Medicine Room 140 1st floor ICTEM building Imperial College Hammersmith London, UK

Dr. Magnani

Luca Magnani, Ph.D
CRUK Fellow/Senior Research Fellow
Department of Surgery and Cancer
Imperial Centre for Translational and Experimental Medicine
Room 140 1st floor ICTEM building
Imperial College Hammersmith
London, UK

MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by the Yin Yang1 molecule?

Response: This study was designed to investigate the evidence of non-genetic mechanisms that could contribute to breast cancer biology. Specifically, we developed a map of regulatory regions from luminal breast cancer patients. Regulatory regions are pieces of DNA that are not transcribed into protein-coding genes but they provide information about where and how much each gene should be activated.

It is worth highlighting that cancer is not only the consequence of gene mutations but also the result of the wrong genes expressed at the wrong time.  To catalogue regulatory regions we looked for specific modifications that are strongly associated with their activity (epigenetic modifications). Doing so we developed the first extensive catalogue  of non-coding DNA regions that might play an essential role in regulating how breast cancer cell behaves. Regulatory regions do their job by interacting with specific molecules called transcription factors. These molecules can read the information stored in these regulatory regions and contribute to regulate gene expression. Yin Yang 1 is one of such molecules and was previously thought as a ambiguous player capable of activating or repressing gene activity.   Continue reading

CRISPR-Gold Has Potential To Edit Brain Genes

MedicalResearch.com Interview with:

Niren Murthy PhD Professor of Bioengineering University of California at Berkeley

Prof. Murthy

Niren Murthy PhD
Professor of Bioengineering
University of California at Berkeley

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In this paper we delivered Cas9 RNP in the brain using a delivery vehicle termed CRISPR-Gold.  We were able to knock out the mGluR5 gene and rescue mice from autism using CRISPR-Gold.  The background here is that there is a great need for safe and effective CRISPR delivery vehicles, and that brain gene editing has great therapeutic potential.  This paper demonstrates for the first time that non-viral delivery of Cas9 RNP into the brain can have therapeutic effects.

MedicalResearch.com: What should clinicians and patients take away from your report?

Response: Brain gene editing has tremendous therapeutic potential, and can be achieved with non-viral Cas9 RNP delivery

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response:   We need to be able to edit the brains of large animals.  The particles will need to be modified for this, we are currently working on this.  GenEdit, a start-up company spun out from our lab, is also working on this.

Disclosures: I was a co-founder of GenEdit, but now have no equity in GenEdit, there should be no conflict of interest

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Bumwhee Lee, Kunwoo Lee, Shree Panda, Rodrigo Gonzales-Rojas, Anthony Chong, Vladislav Bugay, Hyo Min Park, Robert Brenner, Niren Murthy, Hye Young Lee. Nanoparticle delivery of CRISPR into the brain rescues a mouse model of fragile X syndrome from exaggerated repetitive behaviours. Nature Biomedical Engineering, 2018; DOI: 10.1038/s41551-018-0252-8

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

 

 

 

 

 

 

Genetic Variants Help Identify Men At Highest Risk of Prostate Cancer

MedicalResearch.com Interview with:

Fredrick R. Schumacher, PhD, MPH. Associate Professor, Department of Population & Quantitative Health Sciences Case Western Reserve University Cleveland

Dr. Schumacher

Fredrick R. Schumacher, PhD, MPH.
Associate Professor, Department of Population & Quantitative Health Sciences
Case Western Reserve University
Cleveland

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Our study examines the genetic underpinnings of prostate cancer initiation using technology to test variants across the genome. Our study focused on men of European ancestry and included over 80,000 men with prostate cancer and 60,000 men without disease. We discovered 63 novel genetic variants associated with prostate cancer risk, which increases our knowledge of prostate cancer genetic risk factors by more than 60%.

A genetic risk score created from the combination of 163 new and known prostate cancer risk variants revealed men with the highest genetic risk score are nearly seven times more likely to develop disease compared to the average man. Additionally, men with the lowest genetic risk score have a 85% risk reduction of developing prostate cancer compared to the average. Lastly, these new discoveries uncover several biological mechanisms involved in the initiation of prostate cancer.

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Possible Sperm Related Cause of Male Infertility Identified

MedicalResearch.com Interview with:

Tomer Avidor-Reiss, Ph.D.  Professor, College of Natural Sciences and Mathematics Department of Biological Sciences University of Toledo Toledo, OH 43606

Dr. Avidor-Reiss

Tomer Avidor-Reiss, Ph.D. 
Professor, College of Natural Sciences and Mathematics
Department of Biological Sciences
University of Toledo
Toledo, OH 43606

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Most dividing cells in the body need exactly two centrioles for normal cell division and development. Abnormalities in centriole number can cause cancer and devastating developmental defects. Because of this importance of centriole number and because all cells originate from the zygote – the product of the sperm and egg – it makes sense that the zygote should possess two centrioles, as well.

However, the egg does not contain any centrioles, so the sperm is the sole contributor of the centrioles; and yet, it is currently thought that the sperm contains only one centriole. This is problematic because supposedly that leaves the zygote with only one centriole, even though it must propagate cells with two centrioles. In the past, we found that insect sperm have an atypical centriole that escaped discovery because it is so different. We therefore hypothesized that humans may also have an atypical sperm centriole.

Our new paper shows that in human sperm there exists, in addition to the known centriole, a second centriole that deviates from the typical structural and composition that is expected from a centriole. Although it looks very different from any centriole ever described, we found that it functions in an in vitro functional assay. Furthermore, during fertilization, it performs the functions traditionally associated with centrioles. Together, this resolves a 50-year-long debate regarding the centrioles of human sperm; the sperm contains two functional centrioles, despite that one is atypical.  Continue reading

Engineered Single Cell ‘Cured’ Patient of CLL

MedicalResearch.com Interview with:

Dr. J Joseph Melenhorst, PhD Director, Product Development & Correlative Sciences laboratories (PDCS) Adjunct Associate Professor Penn Medicine Center for Cellular Immunotherapies University of Pennsylvania

Dr. Melenhorst

Dr. J Joseph Melenhorst, PhD
Director, Product Development & Correlative Sciences laboratories (PDCS)
Adjunct Associate Professor
Penn Medicine
Center for Cellular Immunotherapies
University of Pennsylvania

MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by CLL and CAR T cells? 

Response: We started treating patients with a form of blood cancer called CLL (chronic lymphocytic leukemia) using a form of gene therapy wherein we engineer the patient’s own immune cells – T cells – with a tumor targeting molecule: The CAR, which stands for chimeric antigen receptor. When we engineer the patient’s immune cells we use a vehicle, in this case virus, that inserts the payload – the CAR – into the patient’s DNA. The virus disappears, and the CAR stays. Where this CAR inserts itself is unpredictable, but we always get stably engineered cells.  Continue reading

Mono Virus Linked To Some Cases of Lupus

MedicalResearch.com Interview with:

John B. Harley, MD, PhD Professor and Director David Glass Endowed Chair Center for Autoimmune Genomics and Etiology (CAGE) Department of Pediatrics University of Cincinnati Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio 45229

Dr. Harley

John B. Harley, MD, PhD
Professor and Director
David Glass Endowed Chair
Center for Autoimmune Genomics and Etiology (CAGE)
Department of Pediatrics
University of Cincinnati
Cincinnati Children’s Hospital Medical Center
Cincinnati, Ohio 45229

MedicalResearch.com: What is the background for this study?

Response: Previous work has shown that Epstein-Barr virus infection is associated with systemic lupus erythematosus and studies of the origins of the autoimmune response have also suggested that the autoimmunity of this disease may originate with the immune response against this virus. In the meantime, many investigators have been studying the genetics of lupus over the past 25 years. They have found about 100 convincing genes that alter the risk of developing lupus.

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Preliminary Results Show NIAGEN® Has Potential To Lower Blood Pressure For Individuals With Pre-Hypertension

MedicalResearch.com Interview with:

Dr. Charles Brenner, PhD Chief Scientific Advisor ChromaDex

Dr. Charles Brenner

Dr. Charles Brenner, PhD
Chief Scientific Advisor
ChromaDex

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Nicotinamide adenine dinucleotide (NAD) is the central regulator of metabolism. NAD is under attack in multiple conditions of metabolic stress and declines in human aging. Thus, using supplements to maintain NAD has emerged as an important strategy to support healthy aging.

There are three vitamin precursors of NAD. However, two of those forms (niacin and nicotinamide) have unwanted side effects and/or inhibit some of the metabolic regulators that can be stimulated by higher NAD. Nicotinamide riboside (NR) is the most recently discovered NAD precursor vitamin. Research has shown that NR boosts NAD more than the other precursors, doesn’t cause flushing, doesn’t inhibit sirtuin enzymes, and that the pathway that converts NR to NAD is turned on in tissues undergoing stress and damage.

Commercialized as NIAGEN®, NR has been clinically proven to significantly increase NAD levels in people as an oral supplement. NIAGEN® is the only NR with published human safety, efficacy and tolerability studies.

The University of Colorado study is the first clinical trial showing that not only does NIAGEN® boost NAD levels, it also may have a beneficial effect on cardiovascular health and function. Continue reading

Two Genes Linked to Severe Nausea and Vomiting in Pregnancy

MedicalResearch.com Interview with:

Marlena Fejzo, PhD Aassociate researche David Geffen School of Medicine UCLA.

Dr. Fejzo

Marlena Fejzo, PhD
Aassociate researche
David Geffen School of Medicine
UCLA. 

MedicalResearch.com: What is the background for this study?

Response: Most women experience some nausea and vomiting of pregnancy, and the worst 2% are diagnosed with Hyperemesis Gravidarum which is associated with poor maternal and fetal outcomes. I had HG in 2 pregnancies. In my second pregnancy my HG was so severe that I could not move without vomiting and did not keep any food or water down for 10 weeks. I was put on a feeding tube, but ultimately lost the baby in the second trimester. I am a medical scientist by training so I looked into what was known about HG. At the time, very little was known, so I decided to study it. I partnered with the Hyperemesis Education and Research Foundation (HER) and we did a survey on family history of .Hyperemesis Gravidarum that provided evidence to support a role for genes. I collected saliva samples from HG patients and their unaffected acquaintances to do a DNA study. Then I partnered with the personal genetics company, 23andMe to do a genome scan and validation study, which identified 2 genes, GDF15 and IGFBP7, linked to HG.

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Activation of Telomerase Will Not Cure Aging

MedicalResearch.com Interview with:

Douglas P. Kiel, MD, MPH Professor of Medicine Harvard Medical School Director Musculoskeletal Research Center Institute for Aging Research, Hebrew SeniorLife Associate Member Broad Institute of Harvard and MIT

Dr. Kiel

Douglas P. Kiel, MD, MPH
Professor of Medicine
Harvard Medical School
Director Musculoskeletal Research Center
Institute for Aging Research, Hebrew SeniorLife
Associate Member Broad Institute of Harvard and MIT 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Why we age? and how we age?, are perennial questions that are of interest to all. The research described in this publication brings together two major and different concepts of aging – epigenetic aging, which is manifested by modifications on DNA and telomere-related aging, which is manifested by shortening of chromosome ends (telomeres).  In our search for genes that could potentially affect epigenetic aging, we detected  a variant of the TERT gene (whose encoded protein, telomerase maintains telomere length) to be associated with accelerated epigenetic aging. TERT is a subunit of the enzyme telomerase which is a widely known enzyme for the following reasons:

1)    Telomerase has been touted as an anti-aging enzyme. It has been called a modern fountain of youth. However, some scientists have pointed out that it is unlikely to become a source of anti-aging therapies (see the review article by de Magalhães JP1, Toussaint in Rejuvenation Research (2004) .https://www.ncbi.nlm.nih.gov/pubmed/15312299)   Our new results gained by the epigenetic clock also indicate that telomerase will not halt organismal aging.

2)    The book “The Telomere Effect” by Nobel prize winner Elizabeth Blackburn and Elissa Epel was on the New York Times best seller list and received substantial news coverage:https://www.cbsnews.com/news/telomere-effect-book-living-younger-healthier-longer/

Our data provides a much needed  understanding of the molecular drivers of the epigenetic clock and reveal a unexpected and paradoxical connection between two seemingly distinct aging clocks: the telomere clock and the epigenetic clock.

Our main finding was that variants in the human telomerase reverse transcriptase gene (TERT) were associated with increased “intrinsic epigenetic aging.” 

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New Technique Allows Mining of Specific Antibodies From B Cells

MedicalResearch.com Interview with:

Dr. Sarav Rajan, PhD Scientist Antibody Discovery and Protein Engineering MedImmune

Dr. Rajan

Dr. Sarav Rajan, PhD Scientist
Antibody Discovery and Protein Engineering
MedImmune

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: During an infection, B cells (a type of white blood cell) create antibodies against antigens present on a pathogen. These cells can be extremely rare, and finding them among the millions of other cells is extremely challenging.

Existing methods to examine B cells require a trade-off: either capture the full sequence repertoire by next-generation sequencing but functionally screen just a subset, or culture a subset of B cells and fully screen them. Instead, our method captures the complete repertoire within a typical blood draw and screens all its members to identify the rare antigen-positive antibodies. Using a new microfluidic approach, we recovered the antibody genes from one million B cells encapsulated in picoliter-scale droplets, breaking through a widely-published view that amplifying from single cells in such small volumes is inefficient. The resulting library seamlessly integrates into our high-throughput screening infrastructure to enable rapid isolation of desired antibodies. Using this method, we were able to isolate a panel of rare cross-reactive antibodies targeting influenza.

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Potential Universal Influenza Vaccine Uses Nanoparticle Technology

MedicalResearch.com Interview with:
“Syringe and Vaccine” by NIAID is licensed under CC BY 2.0Dr. Lei Deng PhD

Postdoctoral researcher
Institute for Biomedical Sciences at Georgia State University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Influenza A viruses evade human herd immunity by genetic hypervariation. Annual influenza epidemics are estimated to cause about 3 to 5 million cases of severe illness, and about 290,000 to 650,000 deaths. Vaccination is still the most effective way to prevent diseases, but current influenza vaccines provide limited protections against mismatched circulating virus strains. This drives scientists to develop universal influenza vaccines that can induce broad immune responses against all influenza A virus infections.

We used biochemistry and nanotechnology to generate a double-layered protein nanoparticle universal influenza vaccine. The layered nanoparticle contains genetically modified influenza virus components without irrelevant carry/structural proteins and chemicals and confers strong and long-lasting immunity in laboratory mice against H1N1, H3N2, H5N1 and H7N9 infections. We also explain the protection mechanism of antibody dependent cell-mediated cytotoxicity (ADCC) and antibody dependent cell-mediated phagocytosis (ADCP) play the main role in the immune protection.  Continue reading

Subtle Motor Biomarker May Be Essential Feature of Autism Spectrum Disorder

Indiana University graduate student Di Wu poses for a portrait in Swain Hall on Friday, Dec. 22, 2017.

Di Wu credit: James Brosher

MedicalResearch.com Interview with:
Di Wu, Msc
PhD candidate at Indiana University
Graduate Research Assistant
Department of Physics
Indiana University Bloomington
Linked-in: www.linkedin.com/in/di-wu-3a197373 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Current clinical diagnosis and evaluations of Autism Spectrum Disorder (ASD). has remained subjective in nature. There is a need to have objective assessments for the disorder. We discovered in this study an important motion feature that was unknown before. This feature provides a clear screening of ASD. It gave a remarkable quantitative connection between the way children with ASD move and their psychiatric scores, like the IQ score and the Vineland Adaptive Behavior Scale. This connection we captured suggests that the motor feature may be an essential core feature characterizing ASD deficits, as well as neurodevelopment in general.

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Melanoma: New Combination Therapy Targets Resistant Tumors

MedicalResearch.com Interview with:

Daniel S. Peeper, PhD Professor of Functional Oncogenomics (VUmc) Member of Oncode Institute Head, Division of Molecular Oncology & Immunology Chair, Scientific Faculty Council Chair, Translational Research Board The Netherlands Cancer Institute Amsterdam The Netherlands

Dr. Peeper

Daniel S. Peeper, PhD
Professor of Functional Oncogenomics (VUmc)
Member of Oncode Institute
Head, Division of Molecular Oncology & Immunology
Chair, Scientific Faculty Council
Chair, Translational Research Board
The Netherlands Cancer Institute
Amsterdam The Netherlands

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: BRAF mutant melanomas are now commonly treated with either immunotherapy or with the combination of BRAFi + MEKi. Recent clinical trials showed that combination checkpoint blockade gives 58% 3 year survival for advanced melanoma. For BRAF+MEKi these numbers are somewhat less impressive. Our study relates to the latter setting.

Clearly, most patients treated with this combination do not experience a durable clinical benefit. We showed previously that resistance to these inhibitors is commonly associated with a striking increase in the number of AXL+ cells; this is the rationale for the current study.  Continue reading

Sugar Compound In Food Products May Have Encouraged Growth of Dangerous C. diff Bacteria

MedicalResearch.com Interview with:

Professor Robert Britton PhD Therapeutic Microbiology Laboratory Department of Molecular Virology and Microbiology Alkek Center for Metagenomics and Microbiome Research Baylor College of Medicine

Prof. Britton

Professor Robert Britton PhD
Therapeutic Microbiology Laboratory
Department of Molecular Virology and Microbiology
Alkek Center for Metagenomics and Microbiome Research
Baylor College of Medicine

MedicalResearch.com Interview: How would you summarise your findings?

Response: As a brief summary of our work, certain strains of Clostridium difficile have emerged in the past 20 years that have resulted in epidemics worldwide, leading to C. difficile becoming one of the most common causes of hospital acquired infections.  Two ribotypes of C. difficile, RT027 and RT078, emerged as key epidemic ribotypes associated with increased disease prevalence and increased mortality in patients.  We found that both of these ribotypes have acquired the ability to consume the disaccharide trehalose by two completely independent mechanisms.  We further show that trehalose enhances disease severity of C. difficile infection in a manner that requires C. difficile to metabolize trehalose in mice.  We also show that trehalose is present in the distal intestine of mice and humans in concentrations that the RT027 ribotype can metabolize.  Because RT027 and RT078 strains were present in clinics at least 10-20 years prior to their becoming epidemic isolates, we looked where people would acquire trehalose in the diet.

In 2000 the FDA approved trehalose for human consumption (EFSA did so in 2001) and based on the GRAS report from the FDA the amount of trehalose predicted to be consumed once released on the market would vastly increase what people get naturally from the diet.  Our data support that these two ribotypes increased in prevalence due to a change in the human diet.

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Early Studies Suggest Blood Pressure Medication Hydralazine May Slow Aging and Neurodegeneration

CrawlingCelegans Wikipedia

Crawling C. elegans
Wikipedia image

MedicalResearch.com Interview with:
Hamid Mirzaei, Ph.D.
Assistant Professor of Biochemistry
University of Texas Southwestern
Department of Biochemistry
Dallas, TX 75390

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Aging is a complex process at the cellular level with distinct organismal phenotypes. Despite millennia-old obsession with aging and relentless pursuits for ways to stop and reverse it, such elixir has not been found due to the complexity of the involved mechanisms and our limited understanding of the processes that lead to aging. Although progress has been made in recent years in slowing down the aging process in model organisms and human cells.

In this study, we report that and FDA approved antihypertensive drug, hydralazine, decelerates aging in C. elegans by mechanisms that seem to resemble dietary restriction. We show that hydralazine increases the median lifespan of the C. elegans by 25% which is comparable to or better than other known antiaging compounds.

We demonstrate that not only hydralazine-treated worms live longer, they appear to be healthier in general. Because aging is directly linked to neurodegenerative diseases, we tested our drug on both in vitro and in vivo models of neurodegenerative diseases using chemical and biological stressors (rotenone and tau fibrils) and show that hydralazine has neuroprotective properties as well.

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Mechanism Identified Linking ASD and Intellectual Disability, Opening Door To Development of Treatment Options

MedicalResearch.com Interview with:

Woo-Yang Kim, Ph.D Associate Professor Department of Developmental Neuroscience  Munroe-Meyer Institute University of Nebraska Medical Center Omaha, NE 68198-5960

Dr-Woo-Yang Kim

Woo-Yang Kim, Ph.D
Associate Professor
Department of Developmental Neuroscience
Munroe-Meyer Institute
University of Nebraska Medical Center
Omaha, NE 68198-5960

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  Autism impairs the ability of individuals to communicate and interact with others. About 75 percent of individuals with autism also have intellectual disability, which is characterized by significant limitations in cognitive functions and adaptive behaviors. While autism and intellectual disability are currently defined using behavioral criteria, little is known about the neuropathogenesis of these conditions.

Recent genetic studies have reported that haploinsufficiency of ARID1B causes autism and intellectual disability. However, the neurobiological function of ARID1B during brain development is unknown.

Our study investigated the neurobiological role of the gene in brain development. Using genetically-modified mice, we found that Arid1b haploinsufficiency leads to an excitation-inhibition imbalance by reducing the number of GABAergic interneurons in the cerebral cortex. Furthermore, we showed that treatment with a GABAA-receptor positive allosteric modulator rescues ASD-like behavior and cognitive dysfunction in Arid1b-haploinsufficient mice, suggesting an association between lower numbers of GABAergic interneurons and behavioral outcomes.

Our findings suggest a pathogenic mechanism for Autism Spectrum Disorder and intellectual disability.

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Single Injection of Klotho Gene Protected Animals From Cognitive Decline

MedicalResearch.com Interview with:

Dr Miguel Chillon PhD Department of Biochemistry and Molecular Biology Universitat Autonoma Barcelona Spain

Dr. Chillon

Dr Miguel Chillon PhD
Department of Biochemistry and Molecular Biology
Universitat Autonoma Barcelona
Spain

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Klotho is a protein with an anti-aging and neuroprotective role. Recent studies show it prevents the development of cognitive problems associated with aging and Alzheimer’s disease. Klotho works mainly by inhibiting the insulin / IGF-1 signaling pathway and decreasing the damage caused by oxidative stress in the brain. One of the latest results revealed that the concentration of Klotho in cerebrospinal fluid is significantly lower in Alzheimer’s patients than in human controls of the same age; and it is lower in the elderly with respect to young adults.

Our study used a gene therapy strategy to introduce the Klotho gene into the Central Nervous System of adult animals. With just a single injection of the Klotho gene, young adult animals were protected over time from the cognitive decline associated with aging in old animals. These exciting results pave the way to further advances in research and the development of a neuroprotective therapy based on Klotho.

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Multispecies Study Identifies Critical Genes in OCD Neurobiology

MedicalResearch.com Interview with:

Hyun Ji Noh PhD Postdoc in the Genome Sequencing and Analysis Program Broad Institute of MIT and Harvard

Dr. Hyun Ji Noh

Hyun Ji Noh PhD
Computational Scientist, Medical and Population Genetics
Broad Institute of MIT and Harvard

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder, characterized by intrusive thoughts and repetitive behaviors. OCD is estimated to affect roughly 80 million people worldwide, but its neurobiology remains poorly understood. To understand the disorder’s underpinnings, we searched for genetic mutations that are associated with OCD.

For this, we first identified 608 genes that were most likely to be important  in OCD – some that have previously been identified in OCD-like behaviors in dogs and mice, and others in human autism, which also involves repetitive behaviors. We compared these genes in 592 people with OCD and 560 people without OCD, and found that 4 of these genes were significantly different between people with and without OCD: NRXN1, HTR2A, CTTNBP2 and REEP3. All of these four genes have important functions in the brain. Specifically, we found that the variants in NRXN1 are likely to change its ability to bind other synaptic proteins. Synaptic proteins link neurons together, and are critical for transmitting signals through the brain. We also found that the variants in CTTNBP2 and REEP3 don’t actually change the proteins made by these genes, but instead probably affect gene regulation (for example, how much of the protein is made). These ‘regulatory’ variants disrupt the binding of transcription factors (proteins that regulate expression of genes in the body) near the gene.

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Mouse Study Shows Intermittent Fasting Limits Obesity and Improves Metabolism

MedicalResearch.com Interview with:

Dr. Hoon-Ki Sung MD PhD Scientist at The Hospital for Sick Children (SickKids) and Assistant Professor in Laboratory Medicine & Pathobiology University of TorontoDr. Hoon-Ki Sung MD PhD Scientist at The Hospital for Sick Children (SickKids) and Assistant Professor in Laboratory Medicine & Pathobiology University of Toronto

Dr. Sung

Dr. Hoon-Ki Sung MD PhD
Scientist at The Hospital for Sick Children (SickKids) and
Assistant Professor in Laboratory Medicine & Pathobiology
University of Toronto 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Despite extensive research and medical interventions, the prevalence of obesity and associated metabolic disease is increasing. More and more studies show that obesity and its associated metabolic problems are often associated with unhealthy lifestyles and eating habits, including frequent eating (non-stop) throughout the day, resulting in a shorter period of physiological fasting. As such, various dietary approaches, such as calorie restriction and intermittent fasting have gained popularity as therapeutic strategies for obesity treatment. Intermittent-fasting is when one temporarily stops eating for a period of time, returns to normal food consumption, and then temporarily stops again.

In our study we examined the effect of an intermittent-fasting regimen, without restricting caloric intake, in mice. We found that an intermittent fasting regimen not only prevented obesity in mice, but also improved metabolism by changing the quality of fat in the body.

Our findings show that the health of the mice is significantly influenced by daily eating patterns. The addition of a ‘stop eating’ period converted inflammatory fat to brown-like (or beige) fat by anti-inflammatory immune cells, meaning it changed bad fat into good fat.

The results are exciting, because they show that weight loss is not the sole benefit of fasting. Fasting also restores the dual function of fat cells, which is to store energy and to release energy.

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Studying Benign Pancreatic Tumors May Lead To Ability To Grow Beta Cells To Reverse Diabetes

MedicalResearch.com Interview with:

Andrew F. Stewart MD Irene and Dr. Arthur M. Fishberg Professor of Medicine Director, Diabetes, Obesity and Metabolism Institute Icahn School of Medicine at Mount Sinai New York, NY 10029

Dr. Stewart

Andrew F. Stewart MD
Irene and Dr. Arthur M. Fishberg Professor of Medicine
Director, Diabetes, Obesity and Metabolism Institute
Institute at the Icahn School of Medicine at Mount Sinai
New York, NY 10029

MedicalResearch.com: What is the background for this study?

Response: Diabetes results ultimately from an inadequate number of insulin-producing “beta” cell in the pancreas.  Ideally, these would regenerate when they are lost or damaged, but unfortunately inducing them to regenerate or proliferate has proven impossible until recently.

In 2015 and others we identified the first class of drugs – the harmine analogues – that are able to induce human beta cells to proliferate.  In this study, we wanted to identify additional pathways that can lead to human beta cell proliferation at higher rates than we had been able to induce with harmine.   For this we turned to a rare type of benign (i.e., not malignant, not cancer) tumor of the beta cells in the pancreas called “insulinomas”. These tiny tumors overproduce insulin and cause hypoglycemia (low blood glucose) which in turn causes seizures, loss of consciousness and confusion.  Once they are discovered, then can easily be removed via laparoscopic surgery, and the person is cured.  Since they are so rare, and since they are benign and easily cured, insulinomas have not been included in large genome sequencing studies of patients wit cancer.  However, we reasoned that they must hold the genomic recipe or wiring diagram for inducing human beta cells to replicate, so we perfumed next-generation DNA and RNA sequencing on a large series (38) of insulinomas.

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Adverse Birth Outcomes and Agricultural Pesticide Use in the San Joaquin Valley of California

MedicalResearch.com Interview with:

Ashley Larsen, PhD Assistant professor Bren School of Environmental Science & Management University of California, Santa Barbara

Dr. Larsen

Ashley Larsen, PhD
Assistant professor
Bren School of Environmental Science & Management
University of California, Santa Barbara

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The relationship between pesticides and adverse birth outcomes has been recognized as an important question for quite some time, and there have been many good studies on the topic. Since randomly exposing people to different levels of pesticides is clearly unethical, researchers focused on the health consequences of non-occupational pesticide exposure often have to choose between detailed studies that follow a couple hundred or couple thousand individuals through pregnancy or larger scale studies that use easier to observe, but less accurate metrics of pesticide exposure (e.g. nearby crops or crop types). Here we tried to provide complementary insight by bridging the gap between detail and scale using detailed pesticide use data and individual birth certificate records for hundreds of thousands of births in an agriculturally dominated region of California. While we found negative effects of pesticide use on birth outcomes including low birth weight, preterm birth and birth abnormalities, these effects were generally in the magnitude of a 5-9% increase in probability of an adverse outcome, and only observed for individuals exposed to very high levels of pesticides.

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H. pylori May Increase Risk of Stomach Cancer By Turning On Subset of Stem Cells

MedicalResearch.com Interview with:
Michael Sigal PhD

Clinical scientist of the Charité — Universitätsmedizin Berlin
Investigator at the Max Planck Institute for Infection Biology 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We have previously found that H. pylori can colonize gastric glands and that in colonized glands the epithelial turnover was increased. We wanted to characterize the mechanisms that control the gland turnover in the stomach.

We found that Axin2, a classic Wnt target gene, marks two different subpopulations of cells with stem cell properties, one of which is Lgr5-positive and the other one Lgr5-negative. Both populations are affected by Rspondin 3, that is produced in myofibroblasts right beneath the stem cell compartment. Rspondin is crucial for stem cell signaling and knockout of Rspondin 3 in myofibroblasts results in loss of Lgr5 and Axin2 expression. Once we increased the bioavailability of Rspondin, that now could also interact with cells outside of the stem cell compartment, we noticed that the number of Axin2 positive stem cells dramatically increased. Of interest, only Lgr5-negative cells expanded in number and proliferate more, while the Lgr5-positive cells remained silenced.

Infection with Helicobacter pylori leads to an expansion of Axin2-positive cells which is driven by increased expression of Rspondin3. Expansion of the long lived stem cell pool could be an explanation for how H. pylori infection increases the risk for gastric cancer.

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