Sleep Deprivation Leads to Build Up of Junk Amyloid in Brain

MedicalResearch.com Interview with:

Nora D. Volkow MD Senior Investigator Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health, Bethesda, MD 20892

Dr. Nora Volkow

Nora D. Volkow MD
Senior Investigator
Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism
National Institutes of Health, Bethesda, MD 20892

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

Response: Findings from animal studies had shown that sleep deprivation increased the content of beta-amyloid in brain, which is a risk factor for Alzheimer’s disease.  We wanted to test whether this also happened in the human brain after one night of sleep deprivation. We found that indeed one night of sleep deprivation led to an accumulation of beta amyloid in the human brain, which suggest that one of the reasons why we sleep is to help clean our brain of degradation products that if not removed are toxic to brain cells.  Continue reading

Combination Inhibitors May Attack More Lung Cancers

MedicalResearch.com Interview with:

Nada Kalaany, PhD Harvard Medical School Boston Children's Hospital  Boston, MA 02115

Dr. Kalaany

Nada Kalaany, PhD
Harvard Medical School
Boston Children’s Hospital
Boston, MA 02115

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

Response: ​ Non-small cell lung cancer (NSCLC) is the predominant form of lung cancer and the leading cause of cancer death in the US and worldwide. Over a quarter of NSCLC harbors activating mutations in the KRAS oncogene, which despite decades of attempts, has proven to be very difficult to target.

KRAS has previously been demonstrated to directly bind to and activate the pro-proliferative kinase PI3K, which is typically activated by insulin/insulin-like growth factor1 (IGF1) signaling. KRAS-PI3K binding is required for KRAS-driven lung cancer formation and progression. However, whether this interaction is sufficient for lung tumor formation and whether additional input is required from insulin/IGF1 signaling, has remained largely controversial.

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Machine Learning Enhances Ability To Predict Survival From Brain Tumors

MedicalResearch.com Interview with:

Lee Cooper, Ph.D. Assistant Professor of Biomedical Informatics Assistant Professor of Biomedical Engineering Emory University School of Medicine - Georgia Institute of Technology

Dr. Cooper

Lee Cooper, Ph.D.
Assistant Professor of Biomedical Informatics
Assistant Professor of Biomedical Engineering
Emory University School of Medicine – Georgia Institute of Technology

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

Response: Gliomas are a form of brain tumor that are often ultimately fatal, but patients diagnosed with glioma may survive as few as 6 months to 10 or more years. Prognosis is an important determinant in selecting treatment, that can range from simply monitoring the disease to surgical removal followed by radiation treatment and chemotherapy. Recent genomic studies have significantly improved our ability to predict how rapidly a patient’s disease will progress, however a significant part of this determination still relies on the visual microscopic evaluation of the tissues by a neuropathologist. The neuropathologist assigns a grade that is used to further refine the prognosis determined by genomic testing.

We developed a predictive algorithm to perform accurate and repeatable microscopic evaluation of glioma brain tumors. This algorithm learns the relationships between visual patterns presented in the brain tumor tissue removed from a patient brain and the duration of that patient’s survival beyond diagnosis. The algorithm was demonstrated to accurately predict survival, and when combining images of histology with genomics into a single predictive framework, the algorithm was slightly more accurate than models based on the predictions of human pathologists. We were also able to identify that the algorithm learns to recognize some of the same tissue features used by pathologists in evaluating brain tumors, and to appreciate their prognostic relevance. Continue reading

Organic Compounds In Bowel Responsible For Longer Healthier Lives in Variety of Species

MedicalResearch.com Interview with:

Daniel Kalman, Ph.D. Department of Pathology and Laboratory Medicine Emory University

Dr. Kalman

Daniel Kalman, Ph.D.
Department of Pathology and Laboratory Medicine
Emory University

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

  1. We think a lot about living longer, but that means we will also have a longer period of frailty and infirmity, which isn’t optimal. Moreover, with geriatric populations projected to expand by 350 fold over the next 40 years, healthcare costs will be unsustainable.
  2. We were interested in understanding how health span of animals is regulated, and whether the microbiota plays a role. The microbiota, which is composed of bacteria inside and on us, when dysregulated (called dysbiosis) contributes to disease; the question we asked was whether it could also contribute to healthy aging, and how.
  3. We showed that animals of widely divergent phyla and separated by hundreds of millions of years of evolutionary time, all utilize indoles to regulate how well they age; in short indoles  make older animals look younger by various metrics, including motility, and fecundity.

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Targeting CD44s May Make Glioblastoma More Sensitive To Clinical Treatment

MedicalResearch.com Interview with:

Chonghui Cheng, M.D., Ph.D. Associate Professor Department of Molecular & Human Genetics Lester & Sue Smith Breast Center Baylor College of Medicine Houston, TX77030

Dr. Cheng

Chonghui Cheng, M.D., Ph.D.
Associate Professor
Department of Molecular & Human Genetics
Lester & Sue Smith Breast Center
Baylor College of Medicine
Houston, TX77030

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

Response: Understanding the mechanisms that give cancer cells the ability to survive and grow opens the possibility of developing improved treatments to control or cure disease. In the case of glioblastoma multiforme, the deadliest type of brain cancer, abnormal EGFR signaling is frequently observed.

Treatment with the EGFR inhibitor erlotinib attempts to kill cancer cells. However, the clinical benefit of treatment with this and other EGFR inhibitors has been limited by the development of drug resistance.

Scientists at Baylor College of Medicine discovered that the molecule CD44s seems to give cancer cells a survival advantage. Eliminating this advantage by reducing the amount of CD44s resulted in cancer cells being more sensitive to the deadly effects of the drug erlotinib.

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Neural Tube Defects in Infants Share Molecular Processes With Neurodegenerative Diseases

MedicalResearch.com Interview with:

Zhiyong Zhao, Ph.D. Associate Professor Department of Obstetrics, Gynecology & Reproductive Sciences University of Maryland School of Medicine Baltimore, MD

Dr. Zhiyong Zhao

Zhiyong Zhao, Ph.D.
Associate Professor
Department of Obstetrics, Gynecology & Reproductive Sciences
University of Maryland School of Medicine
Baltimore, MD

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

Response: Diabetes in early pregnancy can cause neural tube defects in fetus. The defects are a result of failure in neural tube closure, due to excess cell death. The aim of this study was to delineate molecular processes that induce cell death.

The main findings of this study are:
(1) Hyperglycemia disrupts protein folding. The misfolded proteins, including the ones that are associated with neurodegenerative diseases, form aggregates, indicating similar molecular processes in both fetal neural tube defects and adult neurodegenerative diseases.
(2) Protein aggregation leads to formation of a neurodegenerative disease-related cell death inducting mechanism.

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Human Placenta May Be Most Vulnerable To Zika In First Trimester

MedicalResearch.com Interview with:

R. Michael Roberts

Dr. R. Michael Roberts

R. Michael Roberts PhD
Curators’ Distinguished Professor
240b Bond Life Sciences Center
Columbia, Missouri 65211-7310

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

Response: My background in placental biology and in communication between the embryo and the mother in early pregnancy made me curious about how the zika virus (ZIKV) crossed the placenta in early pregnancy to cause microcephaly. My group had been working on a laboratory model for placental trophoblast for over 10 years. We generate trophoblast from human pluripotent cells (embryonic stem cells and induced pluripotent stem cells) by exposing them to the growth factor BMP4 and two pharmaceuticals that inhibit the signaling pathways necessary to maintain pluripotency. I was curious to determine whether or not ZIKV could infect these cells, replicate, and release infectious virus, because work from my collaborator Yoel Sadovsky at the University of Pittsburgh indicated that the mature placenta was likely to be resistant to infection.

MedicalResearch.com: What are the main findings?

Response: There are, I believe two striking outcomes from this work.

One is that the results indicate that the human placenta is likely most vulnerable to infection by Zika during the first trimester. We also suggest that women whose fetus is affected from an infection occurring later in pregnancy likely had a past dengue infection. The second striking result is that the African strain of Zika may have greater virulence towards early placenta than the Asian strains, such as the ones that have spread in the New World.

The work with the virus only began when we realized that term trophoblasts lacked expression of the genes that encode the protein factors that promote flavivirus infection (ZIKV is a flavivirus, like dengue, West Nile virus), e.g. TYRO3, AXL, MERTK, and also had a poised innate immune system that would counteract virus replication. Conversely, the trophoblasts we create from embryonic stem cells had the factors that would promote virus uptake, but seemed ill-prepared to counteract virus replication once infection occurred. In other words, the early placental trophoblasts were potentially more susceptible to infection. We confirmed this hypothesis with two strains of ZIKV (an Asian strain related to the one encountered in Brazil, and an African strain often considered to be relatively benign). What was unexpected was the African strain appeared to be more virulent than the Asian strain.

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

Response: Whether the early placenta could be protected by some sort of immune therapy or by prior vaccination of the mother is clearly uncertain at present. Vaccination programs have not been altogether successful when used to protect against Dengue, which is a virus related to ZIKV.

There is evidence that the early placenta is also permissive to other viruses, such as Rubella. Also there is a very interesting paper in the Journal of the American medical Association by Honein et al. that was published on December 15, 2016. In this study, the overall risk for microcephaly and other brain abnormalities in infants born to a large cohort of U.S. women exposed to ZIKV while traveling (n = 442) was 5.9 % (18), and, of these, there were no cases noted among the women known to have been infected during their second or third trimesters. In Brazil, women appear to be at risk for fetal infections by ZIKV throughout their pregnancies but this may be because they had experienced an earlier infection by Dengue. I have discussed this puzzle in the paper.

I have no disclosures to make, nor conflicts of interest regarding the research or this response to your queries.

Citation:

PNAS Plus – Biological Sciences – Applied Biological Sciences:
Megan A. Sheridan, Dinar Yunusov, Velmurugan Balaraman, Andrei P. Alexenko, Shinichiro Yabe, Sergio Verjovski-Almeida, Danny J. Schust, Alexander W. Franz, Yoel Sadovsky, Toshihiko Ezashi, and R. Michael Roberts
Vulnerability of primitive human placental trophoblast to Zika virus PNAS 2017 114 (9) E1587-E1596; published ahead of print February 13, 2017, doi:10.1073/pnas.1616097114

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

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Anti-Cancer Agent May Have Simultaneous Regenerative Properties

MedicalResearch.com Interview with:

Lawrence Lum, Ph.D. Associate Professor Virginia Murchison Linthicum Scholar in Medical Research UT Southwestern Medical Center

Dr. Lum

Lawrence Lum, Ph.D.
Associate Professor
Virginia Murchison Linthicum Scholar in Medical Research
UT Southwestern Medical Center

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

Response: Scarring of the adult heart due to excessive fibrotic responses is common after a heart attack, or following radiation therapy for the treatment of certain cancers. We have identified an anti-cancer agent currently in clinical development called WNT-974 that decreases fibrotic responses and improves heart function following myocardial infarction in mice. This unexpected observation was the outcome of a study focused on identifying unwanted adult tissue toxicities associated with this class of chemicals.

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Parents Can Encourage Children To Enter and Succeed in STEM Studies

MedicalResearch.com Interview with:

Janet Shibley Hyde Evjue-Bascom Professor Helen Thompson Woolley Professor of Psychology and Gender & Women’s Studies Director, Center for Research on Gender & Women University of Wisconsin Madison, WI

Dr. Janet Shibley Hyde

Janet Shibley Hyde
Evjue-Bascom Professor
Helen Thompson Woolley Professor of
Psychology and Gender & Women’s Studies
Director, Center for Research on Gender & Women
University of Wisconsin
Madison, WI

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

Response: The background is that, in the U.S. and many other Western nations, we don’t have enough people going into STEM fields (Science, Technology, Engineering, and Mathematics). Innovations in STEM fields are enormously important in 21st century economies. So, we need to encourage more people to go into STEM fields. To do that, they have to major in a STEM field in college, and to do that, they need to prepare in high school.

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Breast Cancer Cells Become Chemotherapy Resistant By Eating Surrounding Stem Cells

MedicalResearch.com Interview with:

Thomas Bartosh Jr, Ph.D. Assistant Professor Medical Physiology Texas A&M Health Science Center

Dr. Thomas Bartosh Jr,

Thomas Bartosh Jr, Ph.D.
Assistant Professor Medical Physiology
Texas A&M Health Science Center

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

Response: One mysterious and devastating aspect of breast cancer is that it can reemerge abruptly, often as metastatic disease, in patients many years after an apparent eradication of the primary tumor. The sudden reappearance of cancer has been termed relapse and is thought to occur because a minimal number of resilient tumor cells are able to evade frontline therapies and linger in an undetectable/dormant state somewhere in the body for an unpredictable amount of time. Then, for reasons that remain unclear, these same dormant cells awaken and rapidly grow, and produce almost invariably fatal cancerous lesions. The therapeutic challenges of tumor dormancy and need to decode the underlying mechanisms involved are apparent.

Cancer cell behavior is strongly influenced by various non-malignant cell types that are found within the tumor mass itself and that help make up the tumor microenvironment (TME). In particular, bone marrow-derived mesenchymal stem/stromal cells (MSCs), which are actively recruited into the tumor stroma, directly interact with carcinoma cells and significantly impact cancer progression, although the role of MSCs in tumor dormancy remains ill-defined.

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