bl Blood Vessels of Obese Teens Age Prematurely By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Blood Vessels of Obese Teens Age PrematurelyCategory: Health NewsCreated: 5/7/2020 12:00:00 AMLast Editorial Review: 5/8/2020 12:00:00 AM Full Article
bl More Guidance on Inpatient Management of Blood Glucose in COVID-19 By www.webmd.com Published On :: Wed, 06 May 2020 12:05:04 EST Two new graphics from Diabetes UK's COVID-19 task force address inpatient use of subcutaneous insulin for managing hyperglycemia and ketoacidosis when intravenous equipment is unavailable. Full Article
bl Gay Blood Donors: Eager to Help, but Face Barriers By www.webmd.com Published On :: Wed, 06 May 2020 15:36:11 EST The FDA is launching a pilot study to determine if a risk-based questionnaire could take the place of the deferral periods. Full Article
bl Blood Thinners Could Boost COVID-19 Survival By www.webmd.com Published On :: Wed, 06 May 2020 17:27:41 EST As more evidence emerges that COVID-19 is tied to an increased risk of dangerous blood clots, new research suggests that giving patients blood thinners may improve their odds of survival. Full Article
bl AHA News: Statins May Do Double Duty on Heart Disease and Cancer By www.medicinenet.com Published On :: Tue, 7 Jan 2020 00:00:00 PDT Title: AHA News: Statins May Do Double Duty on Heart Disease and CancerCategory: Health NewsCreated: 1/6/2020 12:00:00 AMLast Editorial Review: 1/7/2020 12:00:00 AM Full Article
bl PMC Adds New Page on Public Access By www.ncbi.nlm.nih.gov Published On :: Thu, 1 Oct 2009 08:00:00 EST A new page, Public Access & PMC, has now been added to the About PMC section of the PubMed Central site. “Public Access & PMC” provides information on the relationship between PMC and the NIH Public Access policy, including the difference between the NIH Public Access journal list and PMC journal list. In particular, authors and publishers should find this new site to be a useful resource. Full Article
bl PMC Now Offers a “Preview” Table of Contents for Embargoed Issues By www.ncbi.nlm.nih.gov Published On :: Wed, 28 Oct 2009 08:00:00 EST For any journal issue that has at least one open access or early access article, PMC is now displaying the table of contents (TOC) in advance of the whole issue becoming available. Not to worry, though—only those articles specified for early release are immediately viewable in PMC. As consistent with the terms of access in the journal agreement, the other articles will only become available on their specified release date, as shown in the TOC below. The journal's accessiblity, as indicated on the PMC Journal list also has not changed; for example, Plant Physiology's embargo period is still 12 months. What has changed is that the issues with “preview” TOCs now additionally appear on the journal's archive page. Publishers and others can rest assured, however, that no access terms for any journal have been changed with the unveiling of this new format. Full Article
bl A New Look and Feel for PMC's Public Access Page By www.ncbi.nlm.nih.gov Published On :: Tue, 14 Sep 2010 08:00:00 EST The Public Access & PMC page has been redesigned for greater clarity and usability. In addition to including a list of the FAQs at the top, the new page features a table illustrating all the ways to find various reference numbers for an article: the PMID, NIHMSID, and most important, the PMCID, which must be used to demonstrate compliance in terms of the NIH Public Access Policy. Full Article
bl JATS-Con 2013 Program is Now Available By www.ncbi.nlm.nih.gov Published On :: Wed, 17 Jul 2013 08:00:00 EST JATS-Con is a conference for users of the Journal Article Tag Suite, that is, users of any of the "NLM DTDs" or NISO Z39.96. JATS-Con will take place on the NIH campus in Bethesda, Maryland on October 22 and 23, 2013.The full program is now available, as are proceedings from previous years. There is no charge for the conference; however, space is limited so registration is required.You may also sign up for a pre-conference tutorial on October 21, 2013. Details are on the Tutorial Registration page. Full Article
bl Citation Exporter Feature Now Available By www.ncbi.nlm.nih.gov Published On :: Tue, 18 Nov 2014 08:00:00 EST PMC is happy to announce the addition of a citation exporter feature. This feature makes it easy to retrieve either styled citations that you can copy/paste into your manuscripts, or to download them into a format compatible with your bibliographic reference manager software.When viewing an Entrez search results page, each result summary will now include a "Citation" link. When, clicked, this will open a pop-up window that you can use to easily copy/paste citations formatted in one of three popular styles: AMA (American Medical Association), MLA (Modern Language Association), or APA (American Psychological Association). In addition, the box has links at the bottom that can be used to download the citation information in one of three machine-readable formats, which most bibliographic reference management software can import.The same citation box can also be invoked from an individual article, either in classic view (with the "Citation" link among the list of formats) or the PubReader view, by clicking on the citation information just below the article title in the banner.These human-readable styled citations, and machine-readable formats, will be available through a public API, and we will be providing more details about that in another announcement, on the pmc-utils-announce mailing list. Please subscribe to that list if you are interested. Full Article
bl Full text now available for OA subset articles, in plain text format By www.ncbi.nlm.nih.gov Published On :: Thu, 5 Feb 2015 08:00:00 EST In order to facilitate text and data mining for articles in the Open Access Subset, we are now providing plain text files for those articles on our FTP site. These files contain the full text of the article, extracted either from the XML source files, or (for those articles that don't have XML) the PDF files. Users are directly and solely responsible for compliance with copyright restrictions and are expected to adhere to the terms and conditions defined by the copyright holder (see the PMC Copyright Notice).These text files are bundled in gzipped archives. Note that these files are quite large (each greater than one gigabyte). They are available for download as: ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/articles.txt.0-9A-B.tar.gz ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/articles.txt.C-H.tar.gz ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/articles.txt.I-N.tar.gz ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/articles.txt.O-Z.tar.gz These files are updated every week, on Saturday.For more information, see the Bulk Packages of OA Articles section of our FTP Service page. Full Article
bl CC0 Filter Now Available By www.ncbi.nlm.nih.gov Published On :: Mon, 23 Nov 2015 08:00:00 EST PMC includes some journals published by US government agencies that make their articles available under a Creative Commons CC0 (public domain) license. Some other journals also apply a CC0 license to selected articles in PMC. All these articles may be used and reproduced without special permission. However, anyone using the material is requested to properly cite and acknowledge the source. You may now search for CC0 articles by using special filters in both PMC (cc0 license[filter]) and PubMed (pmc cc0 license[filter]). These filters are based on license information that is provided to PMC by publishers and encoded as machine-readable identifiers in the source XML of each article. For more information, see the Open Access Subset page. Please bear in mind that these articles, although made available under a CC0 license, may still contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright. Full Article
bl NIH Author Manuscripts Available for Text Mining By www.ncbi.nlm.nih.gov Published On :: Mon, 11 Jan 2016 08:00:00 EST NIH-supported scientists have made over 300,000 author manuscripts available in PMC. Now NIH is making these papers accessible to the public in a format that will allow robust text analyses.You can download the PMC collection of NIH-supported author manuscripts as a package in either XML or plain-text format at ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/manuscript/. The collection encompasses all NIH manuscripts posted to PMC that were published in July 2008 or later. While the public can access the manuscripts’ full text and accompanying figures, tables, and multimedia via the PMC website, the newly available XML and plain-text files include full text only. In addition to text mining, the files may be used consistent with the principles of fair use under copyright law.Please note that these author manuscript files are not part of the PMC Open Access Subset.The NIH Office of Extramural Research developed this resource to increase the impact of NIH funding. Through this collection, scientists will be able to analyze these manuscripts, further apply NIH research findings, and generate new discoveries.For more information, please visit the PMC author manuscript collection webpage. Full Article
bl Public Access Expansion and PMC By www.ncbi.nlm.nih.gov Published On :: Thu, 24 Mar 2016 08:00:00 EST Last month marked the third anniversary of the White House’s Office of Science and Technology Policy (OSTP) memorandum directing Federal agencies with more than $100 million in annual research and development (R&D) expenditures to develop plans for increasing public access to the results of the research they support, including scholarly publications. As a result of this directive, in 2015, PMC started providing support as a public access repository for funding agencies beyond the National Institutes of Health (NIH) and Howard Hughes Medical Institute (HHMI).As of March 2015, the following additional agencies are using the NIH Manuscript Submission (NIHMS) system to facilitate the deposit in PMC of peer-reviewed manuscripts that fall under their public access policies: Agency for Healthcare Research Quality (AHRQ/HHS) Centers for Disease Control and Prevention (CDC/HHS), Food and Drug Administration (FDA/HHS), National Institute of Standards and Technology (NIST), and U.S. Department of Veterans Affairs (VA) Additionally, the following additional HHS and other federal agencies have announced public access plans and committed to using PMC as the repository for agency-funded publications: Administration for Community Living (ACL/HHS) Assistant Secretary for Preparedness and Response (ASPR/HHS) Environmental Protection Agency (EPA) National Aeronautics and Space Administration (NASA) PMC will continue to update the list of participating funding agencies at Public Access and PMC as these agencies begin implementation of their policies.More information about the current status of public access expansion as a result of the OSTP memo can be found on the White House blog. Full Article
bl PMC Adds Support for Machine-Readable Clinical Trial Information By www.ncbi.nlm.nih.gov Published On :: Mon, 7 Jan 2019 08:00:00 EST Machine-readability of scholarly outputs is critical to supporting large-scale analysis of the scientific literature. To that end, PMC’s Tagging Guidelines and internal processes have been updated to support the JATS4R recommendations for tagging clinical trial information. NLM encourages PMC-participating publishers, journals, and data providers to review this guidance. Please contact us at pubmedcentral@ncbi.nlm.nih.gov if you have any questions. Full Article
bl PMC Tagging Guidance for Peer Review Documents Now Available By www.ncbi.nlm.nih.gov Published On :: Wed, 31 Jul 2019 08:00:00 EST Peer review documents, including review reports and editor decision letters, are increasingly being published along with the articles they review. This practice is intended to make the publishing process more transparent. To support these efforts, PMC’s Tagging Guidelines have been updated to include the tagging of peer review documents. NLM encourages PMC-participating publishers, journals, and data providers to review this guidance. Please contact us at pubmedcentral@ncbi.nlm.nih.gov if you have any questions. Full Article
bl PMC Collaborating with Publishers in Response to COVID-19 Public Health Emergency By www.ncbi.nlm.nih.gov Published On :: Thu, 26 Mar 2020 08:00:00 EST On March 13, 2020, the National Science and Technology Advisors from a dozen countries, including the United States, called on publishers to voluntarily agree to make their COVID-19 and coronavirus-related publications and associated data immediately accessible in PubMed Central (PMC) and other appropriate public repositories to support the ongoing public health emergency response efforts.For more information on which publishers have responded to this call and how to discover COVID-19 and coronavirus-related publications in PMC, see the main COVID-19 Initiative page.A FAQ is also available. If you have questions not addressed in the FAQ, please contact pmc-phe@ncbi.nlm.nih.gov.You can learn more about how this initiative fits into the wider NLM response to the current public health emergency in Dr. Patti Brennan's post, "How Does a Library Respond to a Global Crisis?" Full Article
bl Intense Exercise Can Trigger Heart Trouble in the Unprepared By www.medicinenet.com Published On :: Tue, 3 Mar 2020 00:00:00 PDT Title: Intense Exercise Can Trigger Heart Trouble in the UnpreparedCategory: Health NewsCreated: 3/2/2020 12:00:00 AMLast Editorial Review: 3/3/2020 12:00:00 AM Full Article
bl Pilates May Be Good Medicine for High Blood Pressure By www.medicinenet.com Published On :: Tue, 7 Apr 2020 00:00:00 PDT Title: Pilates May Be Good Medicine for High Blood PressureCategory: Health NewsCreated: 4/6/2020 12:00:00 AMLast Editorial Review: 4/7/2020 12:00:00 AM Full Article
bl Blood Sugar Control May Aid Stroke Recovery in Diabetes Patients By www.medicinenet.com Published On :: Tue, 31 Mar 2020 00:00:00 PDT Title: Blood Sugar Control May Aid Stroke Recovery in Diabetes PatientsCategory: Health NewsCreated: 3/30/2020 12:00:00 AMLast Editorial Review: 3/31/2020 12:00:00 AM Full Article
bl Modern Livestock Farming Can Pose Public Health Risk By www.medicinenet.com Published On :: Fri, 8 May 2020 00:00:00 PDT Title: Modern Livestock Farming Can Pose Public Health RiskCategory: Health NewsCreated: 5/7/2020 12:00:00 AMLast Editorial Review: 5/8/2020 12:00:00 AM Full Article
bl Don't Use Pricey New HIV PrEP Drug When Generics Available: Study By www.medicinenet.com Published On :: Tue, 10 Mar 2020 00:00:00 PDT Title: Don't Use Pricey New HIV PrEP Drug When Generics Available: StudyCategory: Health NewsCreated: 3/9/2020 12:00:00 AMLast Editorial Review: 3/10/2020 12:00:00 AM Full Article
bl Heavy Pot Use Linked to Mental Problems, Even After Quitting By www.medicinenet.com Published On :: Fri, 1 May 2020 00:00:00 PDT Title: Heavy Pot Use Linked to Mental Problems, Even After QuittingCategory: Health NewsCreated: 4/30/2020 12:00:00 AMLast Editorial Review: 5/1/2020 12:00:00 AM Full Article
bl Blood Pressure Dips Upon Standing Might Not Be as Dangerous as Thought By www.medicinenet.com Published On :: Wed, 29 Jan 2020 00:00:00 PDT Title: Blood Pressure Dips Upon Standing Might Not Be as Dangerous as ThoughtCategory: Health NewsCreated: 1/28/2020 12:00:00 AMLast Editorial Review: 1/29/2020 12:00:00 AM Full Article
bl Your Best Bet Against Heart Attack, Stroke? Lower Blood Pressure By www.medicinenet.com Published On :: Fri, 21 Feb 2020 00:00:00 PDT Title: Your Best Bet Against Heart Attack, Stroke? Lower Blood PressureCategory: Health NewsCreated: 2/20/2020 12:00:00 AMLast Editorial Review: 2/21/2020 12:00:00 AM Full Article
bl AHA News: These Stroke Survivors May Not Be Prescribed Enough Blood Pressure Meds By www.medicinenet.com Published On :: Mon, 24 Feb 2020 00:00:00 PDT Title: AHA News: These Stroke Survivors May Not Be Prescribed Enough Blood Pressure MedsCategory: Health NewsCreated: 2/21/2020 12:00:00 AMLast Editorial Review: 2/24/2020 12:00:00 AM Full Article
bl New Moms Need to Watch Out for High Blood Pressure By www.medicinenet.com Published On :: Wed, 26 Feb 2020 00:00:00 PDT Title: New Moms Need to Watch Out for High Blood PressureCategory: Health NewsCreated: 2/25/2020 12:00:00 AMLast Editorial Review: 2/26/2020 12:00:00 AM Full Article
bl AHA News: Could Sunshine Lower Blood Pressure? Study Offers Enlightenment By www.medicinenet.com Published On :: Mon, 2 Mar 2020 00:00:00 PDT Title: AHA News: Could Sunshine Lower Blood Pressure? Study Offers EnlightenmentCategory: Health NewsCreated: 2/28/2020 12:00:00 AMLast Editorial Review: 3/2/2020 12:00:00 AM Full Article
bl U.S. Deaths From High Blood Pressure Soar, Especially in the South: Study By www.medicinenet.com Published On :: Tue, 24 Mar 2020 00:00:00 PDT Title: U.S. Deaths From High Blood Pressure Soar, Especially in the South: StudyCategory: Health NewsCreated: 3/23/2020 12:00:00 AMLast Editorial Review: 3/24/2020 12:00:00 AM Full Article
bl Up Your Steps to Lower Blood Pressure, Heart Study Suggests By www.medicinenet.com Published On :: Fri, 27 Mar 2020 00:00:00 PDT Title: Up Your Steps to Lower Blood Pressure, Heart Study SuggestsCategory: Health NewsCreated: 3/26/2020 12:00:00 AMLast Editorial Review: 3/27/2020 12:00:00 AM Full Article
bl 24 Best Foods for Blood Circulation By www.medicinenet.com Published On :: Thu, 9 Apr 2020 00:00:00 PDT Title: 24 Best Foods for Blood CirculationCategory: Health and LivingCreated: 4/9/2020 12:00:00 AMLast Editorial Review: 4/9/2020 12:00:00 AM Full Article
bl Low Blood Pressure (Hypotension) By www.medicinenet.com Published On :: Tue, 14 Apr 2020 00:00:00 PDT Title: Low Blood Pressure (Hypotension) Category: Diseases and ConditionsCreated: 12/31/1997 12:00:00 AMLast Editorial Review: 4/14/2020 12:00:00 AM Full Article
bl Blood Pressure Spikes at Night May Spell Trouble for Brain By www.medicinenet.com Published On :: Mon, 20 Apr 2020 00:00:00 PDT Title: Blood Pressure Spikes at Night May Spell Trouble for BrainCategory: Health NewsCreated: 4/17/2020 12:00:00 AMLast Editorial Review: 4/20/2020 12:00:00 AM Full Article
bl Vaginal Bleeding By www.medicinenet.com Published On :: Tue, 11 Feb 2020 00:00:00 PDT Title: Vaginal BleedingCategory: Diseases and ConditionsCreated: 7/4/2001 12:00:00 AMLast Editorial Review: 2/11/2020 12:00:00 AM Full Article
bl Sublocade (buprenorphine extended release) By www.medicinenet.com Published On :: Fri, 17 Apr 2020 00:00:00 PDT Title: Sublocade (buprenorphine extended release)Category: MedicationsCreated: 4/17/2020 12:00:00 AMLast Editorial Review: 4/17/2020 12:00:00 AM Full Article
bl Sublocade (buprenorphine) By www.medicinenet.com Published On :: Tue, 21 Apr 2020 00:00:00 PDT Title: Sublocade (buprenorphine)Category: MedicationsCreated: 4/21/2020 12:00:00 AMLast Editorial Review: 4/21/2020 12:00:00 AM Full Article
bl Health Tip: Coping With Winter Nosebleeds By www.medicinenet.com Published On :: Fri, 10 Jan 2020 00:00:00 PDT Title: Health Tip: Coping With Winter NosebleedsCategory: Health NewsCreated: 1/10/2020 12:00:00 AMLast Editorial Review: 1/10/2020 12:00:00 AM Full Article
bl Allergy Med Singulair to Get 'Black Box' Warning Over Psych Side Effects: FDA By www.medicinenet.com Published On :: Thu, 5 Mar 2020 00:00:00 PDT Title: Allergy Med Singulair to Get 'Black Box' Warning Over Psych Side Effects: FDACategory: Health NewsCreated: 3/4/2020 12:00:00 AMLast Editorial Review: 3/5/2020 12:00:00 AM Full Article
bl More Hot Flashes Could Mean Higher Odds for Heart Trouble By www.medicinenet.com Published On :: Tue, 24 Sep 2019 00:00:00 PDT Title: More Hot Flashes Could Mean Higher Odds for Heart TroubleCategory: Health NewsCreated: 9/24/2019 12:00:00 AMLast Editorial Review: 9/24/2019 12:00:00 AM Full Article
bl Pot Use Among U.S. Seniors Nearly Doubled in 3 Years By www.medicinenet.com Published On :: Tue, 25 Feb 2020 00:00:00 PDT Title: Pot Use Among U.S. Seniors Nearly Doubled in 3 YearsCategory: Health NewsCreated: 2/24/2020 12:00:00 AMLast Editorial Review: 2/25/2020 12:00:00 AM Full Article
bl AHA News: Dropping Blood Pressure May Predict Frailty, Falls in Older People By www.medicinenet.com Published On :: Tue, 31 Mar 2020 00:00:00 PDT Title: AHA News: Dropping Blood Pressure May Predict Frailty, Falls in Older PeopleCategory: Health NewsCreated: 3/30/2020 12:00:00 AMLast Editorial Review: 3/31/2020 12:00:00 AM Full Article
bl Aftermath of Seizures Troubling for Those With Epilepsy By www.medicinenet.com Published On :: Mon, 20 Apr 2020 00:00:00 PDT Title: Aftermath of Seizures Troubling for Those With EpilepsyCategory: Health NewsCreated: 4/17/2020 12:00:00 AMLast Editorial Review: 4/20/2020 12:00:00 AM Full Article
bl Supreme Court Justice Ginsberg Treated for Gallbladder Infection By www.medicinenet.com Published On :: Wed, 6 May 2020 00:00:00 PDT Title: Supreme Court Justice Ginsberg Treated for Gallbladder InfectionCategory: Health NewsCreated: 5/5/2020 12:00:00 AMLast Editorial Review: 5/6/2020 12:00:00 AM Full Article
bl Dangerously Hot Days for U.S. Farm Workers Could Double by 2050 By www.medicinenet.com Published On :: Wed, 6 May 2020 00:00:00 PDT Title: Dangerously Hot Days for U.S. Farm Workers Could Double by 2050Category: Health NewsCreated: 5/5/2020 12:00:00 AMLast Editorial Review: 5/6/2020 12:00:00 AM Full Article
bl Tukysa Approved for Unresectable, Metastatic HER2-Positive Breast Cancer By www.medicinenet.com Published On :: Tue, 21 Apr 2020 00:00:00 PDT Title: Tukysa Approved for Unresectable, Metastatic HER2-Positive Breast CancerCategory: Health NewsCreated: 4/20/2020 12:00:00 AMLast Editorial Review: 4/21/2020 12:00:00 AM Full Article
bl Parent or Sibling With Colon Cancer? You May Need Colonoscopy Earlier By www.medicinenet.com Published On :: Tue, 21 Apr 2020 00:00:00 PDT Title: Parent or Sibling With Colon Cancer? You May Need Colonoscopy EarlierCategory: Health NewsCreated: 4/20/2020 12:00:00 AMLast Editorial Review: 4/21/2020 12:00:00 AM Full Article
bl Bacterial Blood Infections Tied to Heightened Colon Cancer Risk By www.medicinenet.com Published On :: Thu, 23 Apr 2020 00:00:00 PDT Title: Bacterial Blood Infections Tied to Heightened Colon Cancer RiskCategory: Health NewsCreated: 4/22/2020 12:00:00 AMLast Editorial Review: 4/23/2020 12:00:00 AM Full Article
bl Erratic Sleep Habits May Boost Risk of Heart Problems: Study By www.medicinenet.com Published On :: Thu, 5 Mar 2020 00:00:00 PDT Title: Erratic Sleep Habits May Boost Risk of Heart Problems: StudyCategory: Health NewsCreated: 3/4/2020 12:00:00 AMLast Editorial Review: 3/5/2020 12:00:00 AM Full Article
bl CDK9 Blockade Exploits Context-dependent Transcriptional Changes to Improve Activity and Limit Toxicity of Mithramycin for Ewing Sarcoma By mct.aacrjournals.org Published On :: 2020-05-04T05:39:42-07:00 There is a need to develop novel approaches to improve the balance between efficacy and toxicity for transcription factor–targeted therapies. In this study, we exploit context-dependent differences in RNA polymerase II processivity as an approach to improve the activity and limit the toxicity of the EWS-FLI1–targeted small molecule, mithramycin, for Ewing sarcoma. The clinical activity of mithramycin for Ewing sarcoma is limited by off-target liver toxicity that restricts the serum concentration to levels insufficient to inhibit EWS-FLI1. In this study, we perform an siRNA screen of the druggable genome followed by a matrix drug screen to identify mithramycin potentiators and a synergistic "class" effect with cyclin-dependent kinase 9 (CDK9) inhibitors. These CDK9 inhibitors enhanced the mithramycin-mediated suppression of the EWS-FLI1 transcriptional program leading to a shift in the IC50 and striking regressions of Ewing sarcoma xenografts. To determine whether these compounds may also be liver protective, we performed a qPCR screen of all known liver toxicity genes in HepG2 cells to identify mithramycin-driven transcriptional changes that contribute to the liver toxicity. Mithramycin induces expression of the BTG2 gene in HepG2 but not Ewing sarcoma cells, which leads to a liver-specific accumulation of reactive oxygen species (ROS). siRNA silencing of BTG2 rescues the induction of ROS and the cytotoxicity of mithramycin in these cells. Furthermore, CDK9 inhibition blocked the induction of BTG2 to limit cytotoxicity in HepG2, but not Ewing sarcoma cells. These studies provide the basis for a synergistic and less toxic EWS-FLI1–targeted combination therapy for Ewing sarcoma. Full Article
bl Identification of ALDH1A3 as a Viable Therapeutic Target in Breast Cancer Metastasis-Initiating Cells By mct.aacrjournals.org Published On :: 2020-05-04T05:39:42-07:00 The development of efficacious therapies targeting metastatic spread of breast cancer to the brain represents an unmet clinical need. Accordingly, an improved understanding of the molecular underpinnings of central nervous system spread and progression of breast cancer brain metastases (BCBM) is required. In this study, the clinical burden of disease in BCBM was investigated, as well as the role of aldehyde dehydrogenase 1A3 (ALDH1A3) in the metastatic cascade leading to BCBM development. Initial analysis of clinical survival trends for breast cancer and BCBM determined improvement of breast cancer survival rates; however, this has failed to positively affect the prognostic milestones of triple-negative breast cancer (TNBC) brain metastases (BM). ALDH1A3 and a representative epithelial–mesenchymal transition (EMT) gene signature (mesenchymal markers, CD44 or Vimentin) were compared in tumors derived from BM, lung metastases (LM), or bone metastases (BoM) of patients as well as mice after injection of TNBC cells. Selective elevation of the EMT signature and ALDH1A3 were observed in BM, unlike LM and BoM, especially in the tumor edge. Furthermore, ALDH1A3 was determined to play a role in BCBM establishment via regulation of circulating tumor cell adhesion and migration phases in the BCBM cascade. Validation through genetic and pharmacologic inhibition of ALDH1A3 via lentiviral shRNA knockdown and a novel small-molecule inhibitor demonstrated selective inhibition of BCBM formation with prolonged survival of tumor-bearing mice. Given the survival benefits via targeting ALDH1A3, it may prove an effective therapeutic strategy for BCBM prevention and/or treatment. Full Article