Title: Raking Your Leaves to the Edge of Your Yard an Invitation to Ticks
Category: Health News
Created: 3/22/2020 12:00:00 AM
Last Editorial Review: 3/23/2020 12:00:00 AM

Title: Your Sushi May Serve Up Parasitic Worms
Category: Health News
Created: 4/13/2020 12:00:00 AM
Last Editorial Review: 4/14/2020 12:00:00 AM

Title: Modern Livestock Farming Can Pose Public Health Risk
Category: Health News
Created: 5/7/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 12:00:00 AM

Title: Allow Dead Men to Be Sperm Donors, Medical Ethicists Say
Category: Health News
Created: 1/22/2020 12:00:00 AM
Last Editorial Review: 1/22/2020 12:00:00 AM

Title: Age Makes the Difference in Sticking With HIV Meds
Category: Health News
Created: 2/12/2020 12:00:00 AM
Last Editorial Review: 2/13/2020 12:00:00 AM

Title: Human Immunodeficiency Virus (HIV)
Category: Diseases and Conditions
Created: 12/31/1997 12:00:00 AM
Last Editorial Review: 3/5/2020 12:00:00 AM

Title: Don't Use Pricey New HIV PrEP Drug When Generics Available: Study
Category: Health News
Created: 3/9/2020 12:00:00 AM
Last Editorial Review: 3/10/2020 12:00:00 AM

Title: Biktarvy (bictegravir, emtricitabine, and tenofovir alafenamide)
Category: Medications
Created: 4/16/2020 12:00:00 AM
Last Editorial Review: 4/16/2020 12:00:00 AM

Title: Genvoya (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide)
Category: Medications
Created: 4/17/2020 12:00:00 AM
Last Editorial Review: 4/17/2020 12:00:00 AM

Title: Lupus (Systemic Lupus Erythematosus or SLE)
Category: Diseases and Conditions
Created: 12/31/1997 12:00:00 AM
Last Editorial Review: 4/9/2020 12:00:00 AM

Title: Are Steroids Really the Answer for Arthritic Knees?
Category: Health News
Created: 4/8/2020 12:00:00 AM
Last Editorial Review: 4/9/2020 12:00:00 AM

Title: High-Tech Prosthetic Arm Melds With Patient's Anatomy
Category: Health News
Created: 4/30/2020 12:00:00 AM
Last Editorial Review: 4/30/2020 12:00:00 AM

Title: Did the Movie 'Joker' Reinforce Prejudice Against Mentally Ill?
Category: Health News
Created: 4/27/2020 12:00:00 AM
Last Editorial Review: 4/28/2020 12:00:00 AM

Title: Recommended Diuretic Drug Tied to Harmful Side Effects
Category: Health News
Created: 2/18/2020 12:00:00 AM
Last Editorial Review: 2/19/2020 12:00:00 AM

Title: AHA News: Being an African American 'Superwoman' Might Come With a Price
Category: Health News
Created: 2/11/2020 12:00:00 AM
Last Editorial Review: 2/12/2020 12:00:00 AM

Title: AHA News: Domestic Abuse May Do Long-Term Damage to Women's Health
Category: Health News
Created: 2/18/2020 12:00:00 AM
Last Editorial Review: 2/19/2020 12:00:00 AM

Title: Endometriosis Risk Can Be Predicted in Young Girls: Study
Category: Health News
Created: 3/10/2020 12:00:00 AM
Last Editorial Review: 3/10/2020 12:00:00 AM

Title: Xiaflex (collagenase clostridium histolyticum)
Category: Medications
Created: 3/3/2020 12:00:00 AM
Last Editorial Review: 3/3/2020 12:00:00 AM

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: Many With Dog Allergies Might Only Be Allergic to Male Dogs
Category: Health News
Created: 1/7/2020 12:00:00 AM
Last Editorial Review: 1/8/2020 12:00:00 AM

Title: Pick Summer Camps Carefully When Your Kid Has Allergies, Asthma
Category: Health News
Created: 2/29/2020 12:00:00 AM
Last Editorial Review: 3/2/2020 12:00:00 AM

Title: An Allergist Offers His Expert Advice for a Sneeze-Free Spring
Category: Health News
Created: 3/7/2020 12:00:00 AM
Last Editorial Review: 3/9/2020 12:00:00 AM

Title: Sinus Surgery (Endoscopic) Procedure
Category: Procedures and Tests
Created: 12/31/1997 12:00:00 AM
Last Editorial Review: 5/5/2020 12:00:00 AM

Title: AHA News: Dropping Blood Pressure May Predict Frailty, Falls in Older People
Category: Health News
Created: 3/30/2020 12:00:00 AM
Last Editorial Review: 3/31/2020 12:00:00 AM

Title: Back in Touch: Technology Restores Hand Sensitivity to Young Quadraplegic
Category: Health News
Created: 4/23/2020 12:00:00 AM
Last Editorial Review: 4/24/2020 12:00:00 AM

Title: What Is a Hepaticojejunostomy?
Category: Procedures and Tests
Created: 4/22/2020 12:00:00 AM
Last Editorial Review: 4/22/2020 12:00:00 AM

Title: How Long Does a Laparoscopic Nissen Fundoplication Last?
Category: Procedures and Tests
Created: 4/29/2020 12:00:00 AM
Last Editorial Review: 4/29/2020 12:00:00 AM

Title: What Is Nasogastric Intubation Used For?
Category: Procedures and Tests
Created: 5/4/2020 12:00:00 AM
Last Editorial Review: 5/4/2020 12:00:00 AM

Title: Supreme Court Justice Ginsberg Treated for Gallbladder Infection
Category: Health News
Created: 5/5/2020 12:00:00 AM
Last Editorial Review: 5/6/2020 12:00:00 AM

Title: Got Flu? Deal Quickly With Complications
Category: Health News
Created: 2/2/2020 12:00:00 AM
Last Editorial Review: 2/3/2020 12:00:00 AM

Title: Flu Season That's Sickened 26 Million May Be at Its Peak
Category: Health News
Created: 2/21/2020 12:00:00 AM
Last Editorial Review: 2/21/2020 12:00:00 AM

Title: Drug Offers Hope Against Tough-to-Treat Chronic Cough
Category: Health News
Created: 2/26/2020 12:00:00 AM
Last Editorial Review: 2/26/2020 12:00:00 AM

Title: Ride-Sharing Services Tied to Rise in Car Crashes
Category: Health News
Created: 4/7/2020 12:00:00 AM
Last Editorial Review: 4/8/2020 12:00:00 AM

Title: Magnetic Brain 'Zap' Shows Promise Against Severe Depression
Category: Health News
Created: 4/7/2020 12:00:00 AM
Last Editorial Review: 4/8/2020 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: Kisqali (ribociclib)
Category: Medications
Created: 4/22/2020 12:00:00 AM
Last Editorial Review: 4/22/2020 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: Vyxeos (daunorubicin and cytarabine)
Category: Medications
Created: 4/24/2020 12:00:00 AM
Last Editorial Review: 4/24/2020 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: Erratic Sleep Habits May Boost Risk of Heart Problems: Study
Category: Health News
Created: 3/4/2020 12:00:00 AM
Last Editorial Review: 3/5/2020 12:00:00 AM

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.

Overexpression of transcription factor 3 in alveolar soft part sarcoma(ASPS) results in upregulation of cell proliferation pathways. No standard treatment algorithm exists for ASPS; multikinase inhibitors[tyrosine kinase inhibitor (TKI)] and immune checkpoint inhibitors (ICI) have shown clinical benefit. To date, no studies have reported on management strategies or sequencing of therapy. We evaluated ASPS treatment patterns and responses in an experimental therapeutics clinic. Genomic and morphoproteomic analysis was performed to further elucidate novel targets. We retrospectively reviewed patients with ASPS treated on clinical trials. Demographic and clinical next-generation sequencing (NGS) profiles were collected. AACR GENIE database was queried to further evaluate aberrations in ASPS. Morphoproteomic analysis was carried out to better define the biology of ASPS with integration of genomic and proteomic findings. Eleven patients with ASPS were identified; 7 received NGS testing and mutations in CDKN2A (n = 1) and hepatocyte growth factor (n = 1) were present. Ten patients were treated with TKIs with stable disease as best response and 4 patients with ICI (three partial responses). Within GENIE, 20 patients were identified harboring 3 called pathogenic mutations. Tumor mutation burden was low in all samples. Morphoproteomic analysis confirmed the expression of phosphorylated c-Met. In addition, fatty acid synthase and phosphorylated-STAT3 were detected in tumor cell cytoplasm and nuclei. Patients with ASPS have a quiescent genome and derive clinical benefit from VEGF-targeting TKIs. Morphoproteomic analysis has provided both additional correlative pathways and angiogenic mechanisms that are targetable for patients with ASPS. Our study suggests that sequential therapy with TKIs and immune checkpoint inhibitors is a reasonable management strategy.

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.

2-fluorofucose (2FF) inhibits protein and cellular fucosylation. Afucosylation of IgG antibodies enhances antibody-dependent cell-mediated cytotoxicity by modulating antibody affinity for FcRIIIa, which can impact secondary T-cell activation. Immune responses toward most common solid tumors are dominated by a humoral immune response rather than the presence of tumor-infiltrating cytotoxic T cells. IgG antibodies directed against numerous tumor-associated proteins are found in the sera of both patients with breast cancer and transgenic mice bearing mammary cancer. We questioned whether 2FF would have antitumor activity in two genetically distinct transgenic models; TgMMTV-neu (luminal B) and C3(1)-Tag (basal) mammary cancer. 2FF treatment significantly improved overall survival. The TgMMTV-neu doubled survival time compared with controls [P < 0.0001; HR, 7.04; 95% confidence interval (CI), 3.31–15.0], and survival was significantly improved in C3(1)-Tag (P = 0.0013; HR, 3.36; 95% CI, 1.58–7.14). 2FF treated mice, not controls, developed delayed-type hypersensitivity and T-cell responses specific for syngeneic tumor lysates (P < 0.0001). Serum IgG from 2FF-treated mice enhanced tumor lysis more efficiently than control sera (P = 0.004). Administration of 2FF for prophylaxis, at two different doses, significantly delayed tumor onset in both TgMMTV-neu; 20 mmol/L (P = 0.0004; HR, 3.55; 95% CI, 1.60–7.88) and 50 mmol/L (P = 0.0002; HR: 3.89; 95% CI, 1.71–8.86) and C3(1)-Tag; 20 mmol/L (P = 0.0020; HR, 2.51; 95% CI, 1.22–5.18), and 50 mmol/L (P = 0.0012; HR, 3.36; 95% CI, 1.57–7.18). Mammary cancer was prevented in 33% of TgMMTV-neu and 26% of C3(1)-Tag. 2FF has potent antitumor effects in mammary cancer models. The agent shows preclinical efficacy for both cancer treatment and prevention.

Physical and chemical DNA-damaging agents are used widely in the treatment of cancer. Double-strand break (DSB) lesions in DNA are the most deleterious form of damage and, if left unrepaired, can effectively kill cancer cells. DNA-dependent protein kinase (DNA-PK) is a critical component of nonhomologous end joining (NHEJ), one of the two major pathways for DSB repair. Although DNA-PK has been considered an attractive target for cancer therapy, the development of pharmacologic DNA-PK inhibitors for clinical use has been lagging. Here, we report the discovery and characterization of a potent, selective, and orally bioavailable DNA-PK inhibitor, M3814 (peposertib), and provide in vivo proof of principle for DNA-PK inhibition as a novel approach to combination radiotherapy. M3814 potently inhibits DNA-PK catalytic activity and sensitizes multiple cancer cell lines to ionizing radiation (IR) and DSB-inducing agents. Inhibition of DNA-PK autophosphorylation in cancer cells or xenograft tumors led to an increased number of persistent DSBs. Oral administration of M3814 to two xenograft models of human cancer, using a clinically established 6-week fractionated radiation schedule, strongly potentiated the antitumor activity of IR and led to complete tumor regression at nontoxic doses. Our results strongly support DNA-PK inhibition as a novel approach for the combination radiotherapy of cancer. M3814 is currently under investigation in combination with radiotherapy in clinical trials.