Title: Get Fit to Cut Your Diabetes Risk During Pregnancy
Category: Health News
Created: 4/27/2018 12:00:00 AM
Last Editorial Review: 4/30/2018 12:00:00 AM

Title: Harms of Banned Pregnancy Drug Linger for Decades in Daughters
Category: Health News
Created: 5/2/2018 12:00:00 AM
Last Editorial Review: 5/3/2018 12:00:00 AM

Title: Device Might Detect Breast Cancer-Linked Swelling Sooner
Category: Health News
Created: 5/3/2018 12:00:00 AM
Last Editorial Review: 5/4/2018 12:00:00 AM

Title: Breast Cancer Prognosis May Be Worse If Diagnosis Follows 'Negative' Mammogram
Category: Health News
Created: 5/3/2018 12:00:00 AM
Last Editorial Review: 5/4/2018 12:00:00 AM

Title: How Much Does Your Kid Weigh? Chances Are, You're Underestimating
Category: Health News
Created: 4/28/2019 12:00:00 AM
Last Editorial Review: 4/29/2019 12:00:00 AM

Title: Most States Restrict Pregnant Women's Advance Directives: Study
Category: Health News
Created: 4/26/2019 12:00:00 AM
Last Editorial Review: 4/29/2019 12:00:00 AM

Title: Study Supports Radiation for Early, Hormone-Driven Breast Cancer
Category: Health News
Created: 4/26/2019 12:00:00 AM
Last Editorial Review: 4/29/2019 12:00:00 AM

Title: One High Dose of Radiation May Be Enough for Early Prostate Cancer
Category: Health News
Created: 4/30/2019 12:00:00 AM
Last Editorial Review: 4/30/2019 12:00:00 AM

Title: Health Tip: Managing Nausea for Cancer Patients
Category: Health News
Created: 4/30/2019 12:00:00 AM
Last Editorial Review: 4/30/2019 12:00:00 AM

Title: Many Cardiologists Ill-Equipped to Treat Heart Disease in Cancer Survivors
Category: Health News
Created: 4/29/2019 12:00:00 AM
Last Editorial Review: 4/30/2019 12:00:00 AM

Title: Gene Therapy May Help Fight Tough-to-Treat Blood Cancer
Category: Health News
Created: 5/1/2019 12:00:00 AM
Last Editorial Review: 5/2/2019 12:00:00 AM

Title: Breast Implants Linked to Cancer Can Still be Sold in U.S.: FDA
Category: Health News
Created: 5/3/2019 12:00:00 AM
Last Editorial Review: 5/3/2019 12:00:00 AM

Title: Mental Prep for Better Performance
Category: Health News
Created: 5/3/2019 12:00:00 AM
Last Editorial Review: 5/3/2019 12:00:00 AM

Title: Device Spots Lymphedema Early in Breast Cancer Patients, to Help Stop It
Category: Health News
Created: 5/2/2019 12:00:00 AM
Last Editorial Review: 5/3/2019 12:00:00 AM

Title: Red Tape Means Many Cancer Patients Get Radiation Treatments Late
Category: Health News
Created: 5/2/2019 12:00:00 AM
Last Editorial Review: 5/3/2019 12:00:00 AM

Title: Will Social Distancing Last Through the Summer?
Category: Health News
Created: 4/27/2020 12:00:00 AM
Last Editorial Review: 4/27/2020 12:00:00 AM

Title: Obamacare May Help Many Laid-Off Workers Get Health Insurance
Category: Health News
Created: 4/29/2020 12:00:00 AM
Last Editorial Review: 4/30/2020 12:00:00 AM

Title: Trump Says Federal Guidelines on Social Distancing Set to Expire
Category: Health News
Created: 4/30/2020 12:00:00 AM
Last Editorial Review: 4/30/2020 12:00:00 AM

Title: Thousands of Health Care Workers Lack Insurance If COVID-19 Strikes: Study
Category: Health News
Created: 4/30/2020 12:00:00 AM
Last Editorial Review: 5/1/2020 12:00:00 AM

Title: Eating Fish in Moderation During Pregnancy Benefits Fetus: Study
Category: Health News
Created: 3/20/2020 12:00:00 AM
Last Editorial Review: 3/23/2020 12:00:00 AM

Title: Could Cellphone, Microwave Radiation During Pregnancy Raise ADHD Risk?
Category: Health News
Created: 3/24/2020 12:00:00 AM
Last Editorial Review: 3/25/2020 12:00:00 AM

Title: Pregnancy Guidelines During COVID-19 Pandemic
Category: Health News
Created: 4/2/2020 12:00:00 AM
Last Editorial Review: 4/2/2020 12:00:00 AM

Title: Pregnancy Complications Raise Future Odds of Preterm Birth: Study
Category: Health News
Created: 5/1/2020 12:00:00 AM
Last Editorial Review: 5/4/2020 12:00:00 AM

Title: Sleep Disturbances May Trigger Migraine
Category: Health News
Created: 12/26/2019 12:00:00 AM
Last Editorial Review: 12/27/2019 12:00:00 AM

Title: Early High School Start Times May Hurt Attendance
Category: Health News
Created: 5/1/2020 12:00:00 AM
Last Editorial Review: 5/4/2020 12:00:00 AM

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.

A deluge of new data does not suggest harm with ACE inhibitors and angiotensin blockers in COVID-19 rates or outcomes but suggests possible differential effects of the two drug classes.

In a sign of the times and things to come, in-person cardiovascular society meetings pivot to virtual events.

Title: AHA News: Statins May Do Double Duty on Heart Disease and Cancer
Category: Health News
Created: 1/6/2020 12:00:00 AM
Last Editorial Review: 1/7/2020 12:00:00 AM

In response to the growing interest in the availability of data associated with articles, PMC is reviewing current practices around data and seeking feedback on how to best serve the data needs of the research community.

As part of these efforts, the PMC policy statement on supplementary data was recently updated to more clearly articulate the requirement that any supplementary data (images, tables, video, or other documents / files) that are associated with an article must be deposited in PMC with an article. The search filter "has suppdata[filter]" can be used in PMC to discover records with associated supplementary data files.

In addition to providing supplementary data with an article, NLM is also encouraging journals and authors to make research data available in a public repository and include the relevant data citation(s) in the paper. Guidance for PMC data providers on tagging data citations is available in the Tagging Guidelines. This guidance is based on the JATS4R recommendations on data citations.

Starting this month, the NIH Manuscript Submission (NIHMS) system will also accept deposits of small datasets accompanying deposits of funded author manuscripts for inclusion of PMC. (Guidance for authors is available in the NIHMS FAQ.)

If you have suggestions on future directions in data for PMC to consider, please let us know at pubmedcentral@ncbi.nlm.nih.gov.

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.

Title: One Dose of HPV Vaccine May Protect Against Cervical Cancer
Category: Health News
Created: 2/10/2020 12:00:00 AM
Last Editorial Review: 2/10/2020 12:00:00 AM

Title: Menopause May Someday Disappear as Women Postpone Pregnancy: Study
Category: Health News
Created: 4/24/2020 12:00:00 AM
Last Editorial Review: 4/27/2020 12:00:00 AM

Title: Ask Grandma to Dance to Boost Her Mood And Strengthen Your Bonds
Category: Health News
Created: 4/17/2020 12:00:00 AM
Last Editorial Review: 4/20/2020 12:00:00 AM

Title: Tukysa Approved for Unresectable, Metastatic HER2-Positive Breast Cancer
Category: Health News
Created: 4/20/2020 12:00:00 AM
Last Editorial Review: 4/21/2020 12:00:00 AM

Title: Parent or Sibling With Colon Cancer? You May Need Colonoscopy Earlier
Category: Health News
Created: 4/20/2020 12:00:00 AM
Last Editorial Review: 4/21/2020 12:00:00 AM

Title: Bacterial Blood Infections Tied to Heightened Colon Cancer Risk
Category: Health News
Created: 4/22/2020 12:00:00 AM
Last Editorial Review: 4/23/2020 12:00:00 AM

Title: FDA Approves Trodelvy for Metastatic Triple-Negative Breast Cancer
Category: Health News
Created: 4/24/2020 12:00:00 AM
Last Editorial Review: 4/24/2020 12:00:00 AM

Title: Could AI Help Doctors Map Out Treatments for Brain Cancers?
Category: Health News
Created: 4/24/2020 12:00:00 AM
Last Editorial Review: 4/27/2020 12:00:00 AM

Title: Shun the Sun to Prevent Skin Cancer
Category: Health News
Created: 5/2/2020 12:00:00 AM
Last Editorial Review: 5/4/2020 12:00:00 AM

Title: Fewer Kids in Cancer Trials, Which Might Not Be a Bad Thing
Category: Health News
Created: 5/5/2020 12:00:00 AM
Last Editorial Review: 5/6/2020 12:00:00 AM

Title: Silence Your Snore, Save Your Romance
Category: Health News
Created: 2/9/2020 12:00:00 AM
Last Editorial Review: 2/10/2020 12:00:00 AM

Title: Restful Romance: Smelling Your Lover's Shirt Can Help You Sleep
Category: Health News
Created: 2/14/2020 12:00:00 AM
Last Editorial Review: 2/14/2020 12:00:00 AM

This first-in-human phase I study evaluated the pharmacokinetics, safety, and preliminary efficacy of telisotuzumab, formerly called ABT-700, an antagonistic antibody directed against c-Met. For dose escalation (3+3 design), 3 to 6 patients with advanced solid tumors were enrolled into four dose cohorts (5–25 mg/kg). In the dose-expansion phase, a subset of patients was prospectively selected for MET amplification (FISH screening). Patients received telisotuzumab intravenously on day 1 every 21 days. For dose expansion, 15 mg/kg was chosen as the dose on the basis of safety, pharmacokinetics, and other data from the escalation cohorts. Forty-five patients were enrolled and received at least one dose of telisotuzumab (dose escalation, n = 15; dose expansion, n = 30). Telisotuzumab showed a linear pharmacokinetics profile; peak plasma concentration was proportional to dose level. There were no acute infusion reactions and no dose-limiting toxicities were observed. The most common treatment-related adverse events included hypoalbuminemia (n = 9, 20.0%) and fatigue (n = 5, 11.1%). By Response Evaluation Criteria In Solid Tumors (RECIST), 4 of 10 (40.0%) patients with MET-amplified tumors had confirmed partial response in target lesions (one ovarian, two gastric, and one esophageal), two (20.0%) had stable disease, three (30.0%) had progressive disease; one patient was unable to be evaluated. Among patients with nonamplified tumors (n = 35), no objective responses were observed; however, 11 patients had stable disease per RECIST criteria. In conclusion, telisotuzumab has an acceptable safety profile with clinical activity observed in patients with MET-amplified advanced solid tumors.

Long noncoding RNAs (lncRNA) have been found to play critical roles in tumorigenesis and the development of various cancers, including hepatocellular carcinoma (HCC). Metastasis associated with lung adenocarcinoma transcript-1 (MALAT1) has been identified as an oncogene and prognostic biomarker in HCC. Here, we demonstrated that MALAT1 expression was obviously high in sorafenib-resistant HCC cells. Furthermore, knockdown of MALAT1 increased sorafenib sensitivity in nonresponsive HCC cells, whereas forced expression of MALAT1 conferred sorafenib resistance to responsive HCC cells in vitro. In addition, loss/gain-of-function assays revealed that MALAT1 promoted cell proliferation, migration, and epithelial–mesenchymal transition in HCC cells. Mechanistically, MALAT1 regulated Aurora-A expression by sponging miR-140-5p, thus promoting sorafenib resistance in HCC cells. Moreover, MALAT1 inhibition enhanced the antitumor efficacy of sorafenib in vivo. Clinically, we found that MALAT1 expression was negatively correlated with miR-140-5p expression but positively correlated with Aurora-A expression in patients with HCC and that upregulated MALAT1 was closely correlated with poor survival outcomes in patients with HCC. These findings indicated that MALAT1 may be a novel target for prognosis prediction and therapeutic strategies in patients with HCC treated with sorafenib.

Expression of the DNA/RNA helicase schlafen family member 11 (SLFN11) has been identified as a sensitizer of tumor cells to DNA-damaging agents including platinum chemotherapy. We assessed the impact of SLFN11 expression on response to platinum chemotherapy and outcomes in patients with metastatic castration-resistant prostate cancer (CRPC). Tumor expression of SLFN11 was assessed in 41 patients with CRPC treated with platinum chemotherapy by RNA sequencing (RNA-seq) of metastatic biopsy tissue (n = 27) and/or immunofluorescence in circulating tumor cells (CTC; n = 20). Cox regression and Kaplan–Meier methods were used to evaluate the association of SLFN11 expression with radiographic progression-free survival (rPFS) and overall survival (OS). Multivariate analysis included tumor histology (i.e., adenocarcinoma or neuroendocrine) and the presence or absence of DNA repair aberrations. Patient-derived organoids with SLFN11 expression and after knockout by CRISPR-Cas9 were treated with platinum and assessed for changes in dose response. Patients were treated with platinum combination (N = 38) or platinum monotherapy (N = 3). Median lines of prior therapy for CRPC was two. Median OS was 8.7 months. Overexpression of SLFN11 in metastatic tumors by RNA-seq was associated with longer rPFS compared with those without overexpression (6.9 vs. 2.8 months, HR = 3.72; 95% confidence interval (CI), 1.56–8.87; P < 0.001); similar results were observed for patients with SLFN11-positive versus SLFN11-negative CTCs (rPFS 6.0 vs. 2.2 months, HR = 4.02; 95% CI, 0.77–20.86; P = 0.002). A prostate-specific antigen (PSA) decline of ≥50% was observed in all patients with SLFN11 overexpression. No association was observed between SLFN11 expression and OS. On multivariable analysis, SLFN11 was an independent factor associated with rPFS on platinum therapy. Platinum response of organoids expressing SLFN11 was reduced after SLFN11 knockout. Our data suggest that SLFN11 expression might identify patients with CRPC with a better response to platinum chemotherapy independent of histology or other genomic alterations. Additional studies, also in the context of PARP inhibitors, are warranted.

KRAS mutation is a negative predictive biomarker of anti-EGFR agents in patients with metastatic colorectal cancer (mCRC), and remains an elusive target. Pelareorep, a double-stranded RNA virus selectively replicates in KRAS-mutated cells, and is synergistic with irinotecan. A dose escalation trial of FOLFIRI/bevacizumab [irinotecan (150–180 mg/m²) and pelareorep (1 x 10¹⁰ TCID₅₀–3 x 10¹⁰ TCID₅₀)] was implemented in adult patients with oxaliplatin refractory/intolerant, KRAS-mutant mCRC. Pelareorep was administered intravenously over 1 hour on days 1–5 every 4 weeks. Additional studies included pharmacokinetics, tumor morphology, and immune responses. Among FOLFIRI-naïve patients, the highest dose of FOLFIRI/bevacizumab (180 mg/m² irinotecan) and pelareorep (3 x 10¹⁰ TCID₅₀) was well tolerated, without a dose-limiting toxicity. At the recommended phase II dose, 3 of 6 patients (50%) had a partial response; the median progression-free and overall survival (PFS, OS) were 65.6 weeks and 25.1 months, respectively. Toxicities included myelosuppression, fatigue, and diarrhea. Transmission electron microscopy revealed viral factories (viral collections forming vesicular structures), at various stages of development. Immunogold staining against viral capsid -1 protein demonstrated viral "homing" in the tumor cells. The nucleus displayed sufficient euchromatin regions suggestive of active transcription. Flow cytometry revealed rapid dendritic cell maturation (48 hours) with subsequent activation of cytotoxic T cells (7 days). The combination of pelareorep with FOLFIRI/bevacizumab is safe. The PFS and OS data are encouraging and deserve further exploration. Pelareorep leads to a clear recurrent immune stimulatory response with cytotoxic T-cell activation, and homes and replicates in the tumor.

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.

TNF-related apoptosis-inducing ligand (TRAIL) and an agonistic antibody against the death-inducing TRAIL receptor 5, DR5, are thought to selectively induce tumor cell death and therefore, have gained attention as potential therapeutics currently under investigation in several clinical trials. However, some tumor cells are resistant to TRAIL/DR5–induced cell death, even though they express DR5. Previously, we reported that DR5 is transported into the nucleus by importin β1, and knockdown of importin β1 upregulates cell surface expression of DR5 resulting in increased TRAIL sensitivity in vitro. Here, we examined the impact of importin β1 knockdown on agonistic anti-human DR5 (hDR5) antibody therapy. Drug-inducible importin β1 knockdown sensitizes HeLa cells to TRAIL-induced cell death in vitro, and exerts an antitumor effect when combined with agonistic anti-hDR5 antibody administration in vivo. Therapeutic importin β1 knockdown, administered via the atelocollagen delivery system, as well as treatment with the importin β inhibitor, importazole, induced regression and/or eradication of two human TRAIL-resistant tumor cells when combined with agonistic anti-hDR5 antibody treatment. Thus, these findings suggest that the inhibition of importin β1 would be useful to improve the therapeutic effects of agonistic anti-hDR5 antibody against TRAIL-resistant cancers.

Dysregulation of DNA methylation is an established feature of breast cancers. DNA demethylating therapies like decitabine are proposed for the treatment of triple-negative breast cancers (TNBC) and indicators of response need to be identified. For this purpose, we characterized the effects of decitabine in a panel of 10 breast cancer cell lines and observed a range of sensitivity to decitabine that was not subtype specific. Knockdown of potential key effectors demonstrated the requirement of deoxycytidine kinase (DCK) for decitabine response in breast cancer cells. In treatment-naïve breast tumors, DCK was higher in TNBCs, and DCK levels were sustained or increased post chemotherapy treatment. This suggests that limited DCK levels will not be a barrier to response in patients with TNBC treated with decitabine as a second-line treatment or in a clinical trial. Methylome analysis revealed that genome-wide, region-specific, tumor suppressor gene–specific methylation, and decitabine-induced demethylation did not predict response to decitabine. Gene set enrichment analysis of transcriptome data demonstrated that decitabine induced genes within apoptosis, cell cycle, stress, and immune pathways. Induced genes included those characterized by the viral mimicry response; however, knockdown of key effectors of the pathway did not affect decitabine sensitivity suggesting that breast cancer growth suppression by decitabine is independent of viral mimicry. Finally, taxol-resistant breast cancer cells expressing high levels of multidrug resistance transporter ABCB1 remained sensitive to decitabine, suggesting that the drug could be used as second-line treatment for chemoresistant patients.