b 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
b How Long Does a Cholecystostomy Tube Stay In? By www.medicinenet.com Published On :: Thu, 7 May 2020 00:00:00 PDT Title: How Long Does a Cholecystostomy Tube Stay In?Category: Procedures and TestsCreated: 5/7/2020 12:00:00 AMLast Editorial Review: 5/7/2020 12:00:00 AM Full Article
b Were You Born in an H1N1 Flu Year or an H3N2? It Matters By www.medicinenet.com Published On :: Wed, 12 Feb 2020 00:00:00 PDT Title: Were You Born in an H1N1 Flu Year or an H3N2? It MattersCategory: Health NewsCreated: 2/11/2020 12:00:00 AMLast Editorial Review: 2/12/2020 12:00:00 AM Full Article
b Flu Season That's Sickened 26 Million May Be at Its Peak By www.medicinenet.com Published On :: Fri, 21 Feb 2020 00:00:00 PDT Title: Flu Season That's Sickened 26 Million May Be at Its PeakCategory: Health NewsCreated: 2/21/2020 12:00:00 AMLast Editorial Review: 2/21/2020 12:00:00 AM Full Article
b azithromycin (Zithromax): Potential COVID-19 Combo Drug By www.medicinenet.com Published On :: Mon, 30 Mar 2020 00:00:00 PDT Title: azithromycin (Zithromax): Potential COVID-19 Combo DrugCategory: MedicationsCreated: 12/31/1997 12:00:00 AMLast Editorial Review: 3/30/2020 12:00:00 AM Full Article
b Many Car Crash Deaths Involve Alcohol Levels Below Legal Limit: Study By www.medicinenet.com Published On :: Tue, 17 Mar 2020 00:00:00 PDT Title: Many Car Crash Deaths Involve Alcohol Levels Below Legal Limit: StudyCategory: Health NewsCreated: 3/16/2020 12:00:00 AMLast Editorial Review: 3/17/2020 12:00:00 AM Full Article
b High Heat, Humidity Could Affect More Than 1.2 Billion People by End of Century By www.medicinenet.com Published On :: Wed, 25 Mar 2020 00:00:00 PDT Title: High Heat, Humidity Could Affect More Than 1.2 Billion People by End of CenturyCategory: Health NewsCreated: 3/24/2020 12:00:00 AMLast Editorial Review: 3/25/2020 12:00:00 AM Full Article
b Women Are Much Safer Drivers Than Men, British Study Finds By www.medicinenet.com Published On :: Tue, 7 Apr 2020 00:00:00 PDT Title: Women Are Much Safer Drivers Than Men, British Study FindsCategory: Health NewsCreated: 4/7/2020 12:00:00 AMLast Editorial Review: 4/7/2020 12:00:00 AM Full Article
b Broiling in a Heat Wave? Wet T-shirt Can Safely Cool You Down By www.medicinenet.com Published On :: Tue, 14 Apr 2020 00:00:00 PDT Title: Broiling in a Heat Wave? Wet T-shirt Can Safely Cool You DownCategory: Health NewsCreated: 4/13/2020 12:00:00 AMLast Editorial Review: 4/14/2020 12:00:00 AM Full Article
b When Booze Labels Carry Health Warnings, Drinking Declines: Study By www.medicinenet.com Published On :: Mon, 4 May 2020 00:00:00 PDT Title: When Booze Labels Carry Health Warnings, Drinking Declines: StudyCategory: Health NewsCreated: 5/4/2020 12:00:00 AMLast Editorial Review: 5/4/2020 12:00:00 AM Full Article
b Have a Hangover? Try This Herbal Remedy By www.medicinenet.com Published On :: Mon, 4 May 2020 00:00:00 PDT Title: Have a Hangover? Try This Herbal RemedyCategory: Health NewsCreated: 5/1/2020 12:00:00 AMLast Editorial Review: 5/4/2020 12:00:00 AM Full Article
b 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
b Cymbalta (duloxetine) By www.medicinenet.com Published On :: Wed, 12 Feb 2020 00:00:00 PDT Title: Cymbalta (duloxetine)Category: MedicationsCreated: 7/11/2007 12:00:00 AMLast Editorial Review: 2/12/2020 12:00:00 AM Full Article
b Wellbutrin (bupropion) By www.medicinenet.com Published On :: Wed, 12 Feb 2020 00:00:00 PDT Title: Wellbutrin (bupropion)Category: MedicationsCreated: 12/31/1997 12:00:00 AMLast Editorial Review: 2/12/2020 12:00:00 AM Full Article
b AHA News: Stroke Survivors Might Need Better Screening for Depression By www.medicinenet.com Published On :: Thu, 13 Feb 2020 00:00:00 PDT Title: AHA News: Stroke Survivors Might Need Better Screening for DepressionCategory: Health NewsCreated: 2/12/2020 12:00:00 AMLast Editorial Review: 2/13/2020 12:00:00 AM Full Article
b Magnetic Brain 'Zap' Shows Promise Against Severe Depression By www.medicinenet.com Published On :: Wed, 8 Apr 2020 00:00:00 PDT Title: Magnetic Brain 'Zap' Shows Promise Against Severe DepressionCategory: Health NewsCreated: 4/7/2020 12:00:00 AMLast Editorial Review: 4/8/2020 12:00:00 AM Full Article
b 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
b 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
b Kisqali (ribociclib) By www.medicinenet.com Published On :: Wed, 22 Apr 2020 00:00:00 PDT Title: Kisqali (ribociclib)Category: MedicationsCreated: 4/22/2020 12:00:00 AMLast Editorial Review: 4/22/2020 12:00:00 AM Full Article
b 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
b FDA Approves Trodelvy for Metastatic Triple-Negative Breast Cancer By www.medicinenet.com Published On :: Fri, 24 Apr 2020 00:00:00 PDT Title: FDA Approves Trodelvy for Metastatic Triple-Negative Breast CancerCategory: Health NewsCreated: 4/24/2020 12:00:00 AMLast Editorial Review: 4/24/2020 12:00:00 AM Full Article
b Vyxeos (daunorubicin and cytarabine) By www.medicinenet.com Published On :: Fri, 24 Apr 2020 00:00:00 PDT Title: Vyxeos (daunorubicin and cytarabine)Category: MedicationsCreated: 4/24/2020 12:00:00 AMLast Editorial Review: 4/24/2020 12:00:00 AM Full Article
b Could AI Help Doctors Map Out Treatments for Brain Cancers? By www.medicinenet.com Published On :: Mon, 27 Apr 2020 00:00:00 PDT Title: Could AI Help Doctors Map Out Treatments for Brain Cancers?Category: Health NewsCreated: 4/24/2020 12:00:00 AMLast Editorial Review: 4/27/2020 12:00:00 AM Full Article
b Kyprolis (carfilzomib) By www.medicinenet.com Published On :: Mon, 27 Apr 2020 00:00:00 PDT Title: Kyprolis (carfilzomib)Category: MedicationsCreated: 4/27/2020 12:00:00 AMLast Editorial Review: 4/27/2020 12:00:00 AM Full Article
b Obamacare May Have Boosted Use of Mammograms By www.medicinenet.com Published On :: Mon, 4 May 2020 00:00:00 PDT Title: Obamacare May Have Boosted Use of MammogramsCategory: Health NewsCreated: 5/1/2020 12:00:00 AMLast Editorial Review: 5/4/2020 12:00:00 AM Full Article
b Fewer Kids in Cancer Trials, Which Might Not Be a Bad Thing By www.medicinenet.com Published On :: Wed, 6 May 2020 00:00:00 PDT Title: Fewer Kids in Cancer Trials, Which Might Not Be a Bad ThingCategory: Health NewsCreated: 5/5/2020 12:00:00 AMLast Editorial Review: 5/6/2020 12:00:00 AM Full Article
b Traveling Abroad? Make Sure Your Measles Shot Is Up to Date By www.medicinenet.com Published On :: Wed, 24 Jul 2019 00:00:00 PDT Title: Traveling Abroad? Make Sure Your Measles Shot Is Up to DateCategory: Health NewsCreated: 7/24/2019 12:00:00 AMLast Editorial Review: 7/24/2019 12:00:00 AM Full Article
b Too Much Super Bowl Can Mean Too Little Sleep By www.medicinenet.com Published On :: Fri, 31 Jan 2020 00:00:00 PDT Title: Too Much Super Bowl Can Mean Too Little SleepCategory: Health NewsCreated: 1/31/2020 12:00:00 AMLast Editorial Review: 1/31/2020 12:00:00 AM Full Article
b 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
b A Consistent Bedtime Is Good for Your Heart By www.medicinenet.com Published On :: Mon, 6 Apr 2020 00:00:00 PDT Title: A Consistent Bedtime Is Good for Your HeartCategory: Health NewsCreated: 4/3/2020 12:00:00 AMLast Editorial Review: 4/6/2020 12:00:00 AM Full Article
b Using Pot to Help You Sleep? It Could Backfire By www.medicinenet.com Published On :: Wed, 15 Apr 2020 00:00:00 PDT Title: Using Pot to Help You Sleep? It Could BackfireCategory: Health NewsCreated: 4/14/2020 12:00:00 AMLast Editorial Review: 4/15/2020 12:00:00 AM Full Article
b First Good Evidence That Brain Hits 'Replay' While You Sleep By www.medicinenet.com Published On :: Wed, 6 May 2020 00:00:00 PDT Title: First Good Evidence That Brain Hits 'Replay' While You SleepCategory: Health NewsCreated: 5/5/2020 12:00:00 AMLast Editorial Review: 5/6/2020 12:00:00 AM Full Article
b Phase I Dose-Escalation and -Expansion Study of Telisotuzumab (ABT-700), an Anti-c-Met Antibody, in Patients with Advanced Solid Tumors By mct.aacrjournals.org Published On :: 2020-05-04T05:39:42-07:00 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. Full Article
b Long Noncoding RNA MALAT1 Contributes to Sorafenib Resistance by Targeting miR-140-5p/Aurora-A Signaling in Hepatocellular Carcinoma By mct.aacrjournals.org Published On :: 2020-05-04T05:39:42-07:00 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. Full Article
b 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
b Anti-KIT DNA Aptamer for Targeted Labeling of Gastrointestinal Stromal Tumor By mct.aacrjournals.org Published On :: 2020-05-04T05:39:42-07:00 Gastrointestinal stromal tumor (GIST), the most common sarcoma, is characterized by KIT protein overexpression, and tumors are frequently driven by oncogenic KIT mutations. Targeted inhibition of KIT revolutionized GIST therapy and ushered in the era of precision medicine for the treatment of solid malignancies. Here, we present the first use of a KIT-specific DNA aptamer for targeted labeling of GIST. We found that an anti-KIT DNA aptamer bound cells in a KIT-dependent manner and was highly specific for GIST cell labeling in vitro. Functionally, the KIT aptamer bound extracellular KIT in a manner similar to KIT mAb staining, and was trafficked intracellularly in vitro. The KIT aptamer bound dissociated primary human GIST cells in a mutation agnostic manner such that tumors with KIT and PDGFRA mutations were labeled. In addition, the KIT aptamer specifically labeled intact human GIST tissue ex vivo, as well as peritoneal xenografts in mice with high sensitivity. These results represent the first use of an aptamer-based method for targeted detection of GIST in vitro and in vivo. Full Article
b SLFN11 Expression in Advanced Prostate Cancer and Response to Platinum-based Chemotherapy By mct.aacrjournals.org Published On :: 2020-05-04T05:39:42-07:00 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. Full Article
b 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
b Inhibition of Importin {beta}1 Augments the Anticancer Effect of Agonistic Anti-Death Receptor 5 Antibody in TRAIL-resistant Tumor Cells By mct.aacrjournals.org Published On :: 2020-05-04T05:39:42-07:00 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. Full Article
b Decitabine Response in Breast Cancer Requires Efficient Drug Processing and Is Not Limited by Multidrug Resistance By mct.aacrjournals.org Published On :: 2020-05-04T05:39:42-07:00 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. Full Article
b Therapeutic and Prophylactic Antitumor Activity of an Oral Inhibitor of Fucosylation in Spontaneous Mammary Cancers By mct.aacrjournals.org Published On :: 2020-05-04T05:39:42-07:00 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. Full Article
b Pharmacologic Inhibitor of DNA-PK, M3814, Potentiates Radiotherapy and Regresses Human Tumors in Mouse Models By mct.aacrjournals.org Published On :: 2020-05-04T05:39:42-07:00 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. Full Article
b Subject Index to Volume 83 (2019) By www.jdentaled.org Published On :: 2019-12-01T06:00:19-08:00 Full Article
b Residents Perspectives on and Application of Dental Public Health Competencies Using Case-Based Methods By www.jdentaled.org Published On :: 2019-12-01T06:00:19-08:00 The aims of this study were to qualitatively assess dental public health (DPH) residents’ perspectives on teaching methods for DPH competencies and to develop and implement a case-based simulation to address those competencies, constructed on the basis of the qualitative assessment. Focus group discussions were conducted with 18 DPH residents enrolled in two university-based DPH programs. Topic areas discussed in the two focus groups were perceived value of DPH competencies, ways to acquire new DPH skills/abilities, and additional skills/abilities needed by DPH residents. The focus groups’ responses showed that the residents felt competent in the analytical thinking competencies such as research methodology and critiquing literature. They emphasized the importance of learning leadership skills and reported feeling somewhat uncertain about their mastery of the policy and advocacy and system evaluation competencies. Of the two distinct categories of DPH skills and competencies— analytical/critical thinking and practical competencies—these residents reported that a greater proportion of time needed to be devoted to integrating the practical competencies into their education. Based on the residents’ feedback, the authors developed a structured seminar series taking a case-based approach to simulate real-world DPH problems, using real and semi-hypothetical planning projects to meet the residents’ perceived needs and covering gaps between didactic learning and practice. Full Article
b Impact of Collaborative Leadership in Dental School Team Clinics By www.jdentaled.org Published On :: 2019-12-01T06:00:18-08:00 Dental students’ ability to critique team performance in dental school team clinics is a key component of dental education. The aim of this study was to determine if students’ perceptions of their team leaders’ openness of communication, cooperative decision making, and well-defined goals were positively related to the students’ improvement-oriented voice behavior and willingness to raise concerns in the clinical environment. This study used a voluntary 12-question survey, distributed via email to all 311 students at the University of Nevada, Las Vegas School of Dental Medicine after completion of the spring 2017 semester. Eighty-seven students responded, for a response rate of 28%. Responses were stratified by team, class year, and gender, and the quantitative distribution of answers to each question was correlated with each other. Team leader collaborative qualities, which included openness for communication, cooperative decision making, and well-defined goals, were found to have a significant positive relationship with students’ willingness to both raise concerns and make suggestions. Additionally, when measured by class year and gender, team differences in voice behavior assessment by students across the teams were found to be independent of class year, and no significant differences were found by gender. These results suggested that, to maintain high levels of communication, proper reporting of concerns, and a high standard of care, dental schools should encourage team leaders to enhance their capacity to present active collaborative behaviors in the school’s clinic. The study also highlighted potential opportunities for further study of faculty traits and development in the dental school team model. Full Article
b Perceptions of Dental Hygienists About Thesis Completion in Graduate Education By www.jdentaled.org Published On :: 2019-12-01T06:00:18-08:00 Few studies have been published on thesis completion experiences of master’s degree students. However, for doctoral students, dissertation completion has been found to be dependent on individual, relational, and institutional factors. The aim of this study was to examine dental hygienists’ perceptions of their experiences completing a thesis as a requirement for an advanced degree. A qualitative phenomenological research design was used utilizing virtual focus groups with a national purposive sample of dental hygienists (n=25) who had graduated from a degree program in which a thesis was a requirement for the degree. Data analysis used an inductive approach to identify themes using Liechty et al.’s framework of individual, relational, and institutional factors impacting completion of a dissertation. Liechty et al.’s framework is based on Vygotsky’s sociocultural theory of learning. In the results, individual factors identified included family/work responsibilities, lack of understanding of the thesis process, time management, health issues, and reaching personal and professional goals. Relational factors focused primarily on positive and negative experiences with the thesis advisor/committee and support from expert peers/family. Institutional factors included the thesis structure, financial concerns, and challenges in recruiting research participants. This study found many factors influencing the thesis experience that may help guide the process in graduate degree programs. In addition, the findings suggest a need to provide mentoring and support for thesis advisors and committee members to more effectively guide students through the thesis process. Effective modifications of these may improve retention of students and facilitate timely completion of thesis research. Full Article
b Learning and Teaching Together to Advance Evidence-Based Clinical Education: A Faculty Learning Community By www.jdentaled.org Published On :: 2019-12-01T06:00:18-08:00 Clinical teaching is a cornerstone of health sciences education; it is also the most challenging aspect. The University of Pittsburgh Schools of Dental Medicine, Nursing, and Pharmacy developed a new evidence-based interprofessional course framed as a faculty learning community (FLC) around the principles of learning in a clinical environment. The aim of this study was to assess the overall effectiveness of this two-semester FLC at four health professions schools in academic year 2014-15. The assessment included anonymous participant surveys in each session and an anonymous end-of-course survey. Thirty-five faculty members from dental, health and rehabilitation sciences, nursing, and pharmacy enrolled in the FLC, with six to 32 enrollees attending each session. All attendees at each session completed the session evaluation surveys, but the attendance rate at each session ranged from 17.1% to 91.4%. Sixteen participants (46%) completed the end-of-course survey. The results showed overall positive responses to the FLC and changes in the participants’ self-reported knowledge. Session surveys showed that the participants found the FLC topics helpful and appreciated the opportunity to learn from each other and the interprofessional nature of the FLC. Responses to the end-of-course survey were in alignment with the individual session surveys and cited specific benefits as being the content, teaching materials, and structured discussions. In additional feedback, participants reported interest to continue as a cohort and to extend the peer-support system beyond the FLC. This outcomes assessment of the first round of the FLC confirmed that this cohort-based faculty development in an interprofessional setting was well received by its participants. Their feedback provided valuable insights for changes to future offerings. Full Article
b Top-Cited Articles from Dental Education Journals, 2009 to 2018: A Bibliometric Analysis By www.jdentaled.org Published On :: 2019-12-01T06:00:18-08:00 The number of citations an article receives is an important indicator to quantify its influence in its field. The aim of this study was to identify and analyze the characteristics of the 50 top-cited articles addressing dental education published in two journals dedicated to dental education (European Journal of Dental Education and Journal of Dental Education). The Web of Science database was searched to retrieve the 50 most-cited articles from the two journals in December 2018. The top-cited articles were analyzed for journal of publication, number of citations, institution and country of origin, year of publication, study type, keywords, theme and subtheme, and international collaborations. The results showed the 50 top-cited articles were cited between 24 and 146 times each. The majority of these top-cited articles (n=34) were published in the Journal of Dental Education. Half (n=25) of the articles were by authors in the U.S. The most common study types were surveys (n=26) and reviews (n=10). The main themes of these top-cited articles were curriculum and learner characteristics. This bibliometric analysis can serve as a reference for recognizing studies with the most impact in the scholarship of dental education. Full Article
b Entrustable Professional Activities in Oral Health for Primary Care Providers Based on a Scoping Review By www.jdentaled.org Published On :: 2019-12-01T06:00:18-08:00 Despite advances in oral health care, inequalities in oral health outcomes persist due to problems in access. With proper training, primary care providers can mitigate this inequality by providing oral health education, screening, and referral to advanced dental treatment. Diverging sets of oral health competencies and guidelines have been released or endorsed by multiple primary care disciplines. The aim of this study was to transform multiple sets of competencies into Entrustable Professional Activities (EPAs) for oral health integration into primary care training. A scoping review of the literature between January 2000 and December 2016 was conducted according to PRISMA methodology to identify all existing sets of competencies. The following primary care disciplines were included in the search: allopathic/osteopathic medical schools and residency programs in family medicine, internal medicine, and pediatrics; physician assistant programs; and nurse practitioner programs. Competencies were compared using the Health Resources and Services Administration Integration of Oral Health and Primary Care Practice competencies as the foundational set and translated into EPAs. The resulting EPAs were tested with a reactor panel. The scoping review produced 1,466 references, of which 114 were selected for full text review. Fourteen competencies were identified as being central to the integration of oral health into primary care. These were converted to seven EPAs for oral health integration into primary care and were mapped onto Accreditation Council for Graduate Medical Education residency competency domains as well to the Association of American Medical Colleges EPAs for graduating medical students. The resulting EPAs delineate the essential, observable work required of primary care providers to ensure that oral health is treated as a critical determinant of overall health. Full Article
b State Licensing Board Requirements for Entry into the Dental Hygiene Profession By jdh.adha.org Published On :: 2020-04-30T12:39:03-07:00 Purpose: The purpose of this study was to identify current requirements for initial licensure and entry into the dental hygiene profession across state dental and dental hygiene licensing boards in the United States.Methods: A non-experimental study design was used to study dental and dental hygiene board licensing requirements in the United States, Puerto Rico and the Virgin Islands. Each regulatory board website was searched for requirements for entry-level dental hygiene licensure. Requirements were recorded on an Excel spreadsheet. State dental practice acts were reviewed to gather further information and 20 regulatory bodies were contacted to verify accuracy. Descriptive statistics were used to analyze data.Results: Information from a total of 52 dental boards (n=52) was examined for this study. Nearly all boards (n=51, 98.1%), with the exception of Alabama, required completion of entry-level education from a CODA accredited dental hygiene program and successful completion of the National Board Dental Hygiene Examination. Most states (n=51, 98.1%), except Delaware, also required a live-patient, a clinical board examination. Application fees ranged from $47.70 to $600. States varied considerably in terms of requirements for background checks, age, military status, and infection control training.Conclusion: Although the majority of regulatory bodies require completion of entry-level dental hygiene education from a CODA accredited program and successful completion of national board and a live-patient, clinical examination, there is considerable variation in other additional requirements for initial dental hygiene licensure. Full Article