Background. There are shortcomings in nurses’ adherence to ethical principles in practice. The present study aims to investigate the effectiveness of teaching nursing ethics via scenario-based learning and group discussion in nurses’ adherence to codes of ethics and patients’ satisfaction with nurses’ performance. Methods. Using a quasiexperimental design, the present study employed questionnaires which measure nurses’ compliance with nursing codes of ethics and patients’ satisfaction with nursing...
Mon Jun 01, 2020 11:20
Background. Flavonoids from a variety of fruits, including açaí, have beneficial antioxidant activity in several diseases, including cancer. Breast cancer is the second most prevalent cancer among Brazilian women. Studies have shown the action of flavonoids on neoplastic cells, as well as on diabetes and neurodegenerative and cardiovascular diseases. Objective. To analyze the relationship between the consumption of açaí and the presence of chronic diseases in women residing in the rural area of São...
Mon Jun 01, 2020 11:20
This study aims to comprehensively investigate whether there are any differences in the degree of biomechanical adaptation according to habituation to different heel heights. The biomechanical characteristics of 54 subjects in 3 groups habituated to three heel heights (low, medium-high, and high heels) were evaluated by the measurement of surface EMG, myotonometer (e.g., measurement of muscle tension), foot pressure, and lumbosacral angle, and comparative analysis was carried out to find out whether...
Mon Jun 01, 2020 11:20
Background. The World Health Organisation estimates that 1.35 million people die as a result of road traffic crashes. Motorcycles as a means of transport are increasingly becoming the preferred and easiest means of transportation for most people in developing countries despite the associated risk. This study determined the prevalence and pattern of motorcycle crashes in Adidome among commercial motorcyclists. Methods. A descriptive, cross-sectional study design was used as 114 commercial motorcyclists...
Mon Jun 01, 2020 11:05
Background. The reports and information on coronavirus are not conspicuously emphasising the possible impact of population density on the explanation of difference in rapid spread and fatality due to the disease and not much has been done on bicountry comparisons. Objective. The study examined the impact of population density on the spread of COVID-19 pandemic in two sociodemographic divergent countries. Methods. The study conducted a scoping review of published and unpublished articles including...
Mon Jun 01, 2020 03:20
Medical laboratory science students (MLSS), likewise health care workers (HCW), invariably get exposed to blood and body fluids (BBF) of patients. The degree of exposure of these students is even worsened due to their inexperience, which is usually revealed during their vocational training programme. This study therefore determined the prevalence of exposure to BBF and its risk factors among MLSS at the University of Health and Allied Sciences (UHAS). A cross-sectional survey was employed using simple...
Mon Jun 01, 2020 03:05
Abstract International surveys find HPV‐negativity in up to 30% of cervical adenocarcinomas. We investigated the pathological diagnosis by expert consensus with immunohistochemistry and presence of somatic mutations in recognised tumour genes in HPV‐positive and negative cervical adenocarcinomas (CADC). A sample was selected of 45 paraffin‐embedded cervical blocks diagnosed locally as usual cervical adenocarcinoma from a global study. These represented different diagnoses made at previous diagnostic...
Sun May 31, 2020 15:54
Purpose:Trials of adoptive natural killer (NK)-cell immunotherapy for hematologic malignancies have thus far shown only marginal effects, despite the potent in vitro antitumor activity of these cells. Homing of infused cells to tumor microenvironments is critical for efficacy, but has not been well characterized. We established a novel method to track and quantify the distribution of adoptively transferred NK cells using rhesus macaques (RM) as a clinically relevant preclinical model. Experimental...
Mon Jun 01, 2020 10:06
Purpose:Few patients with metastatic triple-negative breast cancer (mTNBC) benefit from immune checkpoint inhibitors (ICI). On the basis of immunotherapy response correlates in other cancers, we evaluated whether high tumor mutational burden (TMB) ≥10 nonsynonymous mutations/megabase and PTEN alterations, defined as nonsynonymous mutations or 1 or 2 copy deletions, were associated with clinical benefit to anti-PD-1/L1 therapy in mTNBC. Experimental Design:We identified patients with mTNBC, who...
Mon Jun 01, 2020 10:06
Mon Jun 01, 2020 10:06
Purpose:Unlike most cancers, no clear epidemiological correlation between diabetes (Db) and malignant glioma progression exists. Because hyperglycemia activates proinflammatory pathways through the receptor for advanced glycation endproducts (RAGE), we hypothesized that Db can also promote malignant glioma progression. Experimental Design:We compared the growth of two phenotypically diverse syngeneic glioma models in control and diabetic mice. Tumor growth and antitumor immune responses were evaluated...
Mon Jun 01, 2020 10:06
Purpose:Patterns of resistance to first-line osimertinib are not well-established and have primarily been evaluated using plasma assays, which cannot detect histologic transformation and have differential sensitivity for copy number changes and chromosomal rearrangements. Experimental Design:To characterize mechanisms of resistance to osimertinib, patients with metastatic EGFR-mutant lung cancers who received osimertinib at Memorial Sloan Kettering Cancer Center and had next-generation sequencing...
Mon Jun 01, 2020 10:06
PARP inhibition induces robust local and systemic antitumor immune responses and curative responses when combined with immune checkpoint blockade in many preclinical studies. However, the combination has not markedly improved antitumor effect compared with individual agents in clinical trials to date. We propose that the data from these trials indicate a lack of synergistic interaction of PARP inhibition and immune checkpoint blockade, with implications for reexamining our current strategies for...
Mon Jun 01, 2020 10:06
Purpose:Recent studies have demonstrated a benefit of adjuvant capecitabine in early breast cancer, particularly in patients with triple-negative breast cancer (TNBC). However, TNBC is heterogeneous and more precise predictive biomarkers are needed. Experimental Design:Tumor tissues collected from TNBC patients in the FinXX trial, randomized to adjuvant anthracycline–taxane–based chemotherapy with or without capecitabine, were analyzed using a 770-gene panel targeting multiple biological mechanisms...
Mon Jun 01, 2020 10:06
Members of the scientific and clinical neuro-oncology community met in April 2019 to discuss the current challenges and opportunities associated with translating basic science discoveries in glioblastoma for improved survival of patients. A summary of key points of these discussions is presented in this article.
Mon Jun 01, 2020 10:06
Purpose:Human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is associated with daily marijuana use and is also increasing in parallel with increased marijuana use in the United States. Our study is designed to define the interaction between cannabinoids and HPV-positive HNSCC. Experimental Design:The expression of cannabinoid receptors CNR1 and CNR2 was analyzed using The Cancer Genome Atlas (TCGA) HNSCC data. We used agonists, antagonists, siRNAs, or shRNA-based models...
Mon Jun 01, 2020 10:06
Purpose:To review key aspects of the design and conduct of early clinical trials (ECT) of immunotherapy agents. Experimental Design:The Methodology for the Development of Innovative Cancer Therapies Task Force 2019 included experts from academia, nonprofit organizations, industry, and regulatory agencies. The review focus was on methodology for ECTs testing immune-oncology therapies (IO) used in combination with other IO or chemotherapy. Results:Although early successes have been seen, the landscape...
Mon Jun 01, 2020 10:06
Purpose:The efficacy of antibody-based therapeutics depends on successful drug delivery into solid tumors; therefore, there is a clinical need to measure intratumoral antibody distribution. This study aims to develop and validate an imaging and computation platform to directly quantify and predict antibody delivery into human head and neck cancers in a clinical study. Experimental Design:Twenty-four patients received systemic infusion of a near-infrared fluorescence-labeled therapeutic antibody...
Mon Jun 01, 2020 10:06
Purpose:The influence of the transcriptional and immunologic context of mutations on therapeutic outcomes with targeted therapy in cancer has not been well defined. BRAF V600E–mutant (BM) colorectal cancer comprises two main transcriptional subtypes, BM1 and BM2. We sought to determine the impact of BM subtype, as well as distinct biological features of those subtypes, on response to BRAF/MEK/EGFR inhibition in patients with colorectal cancer. Patients and Methods:Paired fresh tumor biopsies were...
Mon Jun 01, 2020 10:06
Purpose:Mesenchymal stem cells (MSCs) show an inherent brain tumor tropism that can be exploited for targeted delivery of therapeutic genes to invasive glioma. We assessed whether a motile MSC-based local immunomodulation is able to overcome the immunosuppressive glioblastoma microenvironment and to induce an antitumor immune response. Experimental Design:We genetically modified MSCs to coexpress high levels of IL12 and IL7 (MSCIL7/12, Apceth-301). Therapeutic efficacy was assessed in two immunocompetent...
Mon Jun 01, 2020 10:06
Purpose:The relevance of the MET/hepatocyte growth factor pathway in endometrial cancer tumor biology supports the clinical evaluation of cabozantinib in this disease. Patients and Methods:PHL86/NCI#9322 (NCT01935934) is a single arm study that evaluated cabozantinib (60 mg once daily) in women with endometrial cancer with progression after chemotherapy. Coprimary endpoints were response rate and 12-week progression-free-survival (PFS). Patients with uncommon histology endometrial cancer (eg, carcinosarcoma...
Mon Jun 01, 2020 10:06
Purpose:Prostate cancers with mutations in genes involved in homologous recombination (HR), most commonly BRCA2, respond favorably to PARP inhibition and platinum-based chemotherapy. We investigated whether other prostate tumors that do not harbor deleterious mutations in these particular genes can similarly be deficient in HR, likely rendering those sensitive to HR-directed therapies. Experimental Design:Homologous recombination deficiency (HRD) levels can be estimated using various mutational...
Mon Jun 01, 2020 10:06
Purpose:Genomic alterations in DNA damage repair (DDR) genes other than BRCA may confer synthetic lethality with PARP inhibition in metastatic castration-resistant prostate cancer (mCRPC). To test this hypothesis, the phase II TRITON2 study of rucaparib included patients with mCRPC and deleterious non-BRCA DDR gene alterations. Patients and Methods:TRITON2 enrolled patients who had progressed on one or two lines of next-generation androgen receptor–directed therapy and one taxane-based chemotherapy...
Mon Jun 01, 2020 10:06
Purpose:Exploitation of altered glycosylation in cancer is a major goal for the design of new cancer therapy. Here, we designed a novel secreted chimeric signal peptide–Galectin-3 conjugate (sGal-3) and investigated its ability to induce cancer-specific cell death by targeting aberrantly N-glycosylated cell surface receptors on cancer cells. Experimental Design:sGal-3 was genetically engineered from Gal-3 by extending its N-terminus with a noncleavable signal peptide from tissue plasminogen activator....
Mon Jun 01, 2020 10:06
Purpose:Concurrent inhibition of mTOR and PI3K led to improved efficacy in preclinical models and provided the rationale for this phase I study of everolimus and buparlisib (BKM120) in patients with advanced solid tumor. Patients and Methods:We used the Bayesian Escalation with Overdose Control design to test escalating doses of everolimus (5 or 10 mg) and buparlisib (20, 40, 60, 80, and 100 mg) in eligible patients. Pharmacokinetic assessment was conducted using blood samples collected on cycle...
Mon Jun 01, 2020 10:06
Purpose:Metabolome analysis is an emerging method that provides insight into intracellular and physiologic responses. Methotrexate (MTX) is an antifolate that suppresses DNA syntheses by inhibiting dihydrofolate reductase. High-dose methotrexate treatment with deferred radiotherapy is a standard protocol in primary central nervous system lymphoma (PCNSL) treatments. However, most cases come to relapse-acquired resistance, in which the role of metabolic pathways is largely unknown. Experimental...
Mon Jun 01, 2020 10:06
Purpose:Patient-reported outcomes (PRO) were evaluated in the phase III IMmotion151 trial (NCT02420821) to inform overall treatment/disease burden of atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (mRCC). Patients and Methods:Patients were randomized 1:1 to receive atezolizumab 1,200 mg intravenous (i.v.) infusions every 3 weeks (q3w) plus bevacizumab 15 mg/kg i.v. q3w or sunitinib 50 mg per day orally 4 weeks on/2 weeks off....
Mon Jun 01, 2020 10:06
Purpose:The potential biological determinants of aggressive prostate cancer in African American (AA) men are unknown. Here we characterize prostate cancer genomic alterations in the largest cohort to date of AA men with clinical follow-up for metastasis, with the aim to elucidate the key molecular drivers associated with poor prognosis in this population. Experimental Design:Targeted sequencing was retrospectively performed on 205 prostate tumors from AA men treated with radical prostatectomy (RP)...
Mon Jun 01, 2020 10:06
Purpose:Preclinical data provide evidence for synergism between HER2-targeted peptide vaccines and trastuzumab. The efficacy of this combination was evaluated in patients with HER2 low-expressing breast cancer in the adjuvant setting. Patients and Methods:A phase IIb, multicenter, randomized, single-blinded, controlled trial enrolled disease-free patients after standard therapy completion (NCT01570036). Eligible patients were HLA-A2, A3, A24, and/or A26+, and had HER2 IHC 1+/2+, FISH nonamplified...
Mon Jun 01, 2020 10:06
Purpose:Molecular mechanisms of acquired resistance to MET tyrosine kinase inhibitors (TKI) are poorly understood. We aimed to characterize the genomic mechanisms of resistance to type I and type II MET TKIs and their impact on sequential MET TKI therapy outcomes in patients with metastatic MET exon 14–mutant NSCLC. Experimental Design:Genomic alterations occurring at the time of progression on MET TKIs were studied using plasma and tissue next-generation sequencing (NGS). Results:A total of...
Mon Jun 01, 2020 10:06
Purpose:In this phase I study (NCT01307267), we evaluated safety, pharmacokinetics, clinical activity, and pharmacodynamics of treatment with utomilumab plus rituximab in patients with relapsed/refractory follicular lymphoma (FL) and other CD20+ non-Hodgkin lymphomas (NHL). Patients and Methods:Primary objectives were to assess treatment safety and tolerability for estimating the MTD, using a modified time-to-event continual reassessment method, and selecting the recommended phase II dose (RP2D)....
Mon Jun 01, 2020 10:06
Purpose:The tumor microenvironment (TME) consists of a heterogenous cellular milieu that can influence cancer cell behavior. Its characteristics have an impact on treatments such as immunotherapy. These features can be revealed with single-cell RNA sequencing (scRNA-seq). We hypothesized that scRNA-seq analysis of gastric cancer together with paired normal tissue and peripheral blood mononuclear cells (PBMC) would identify critical elements of cellular deregulation not apparent with other approaches....
Mon Jun 01, 2020 10:06
Purpose:Most ALK-positive lung cancers will develop ALK-independent resistance after treatment with next-generation ALK inhibitors. MET amplification has been described in patients progressing on ALK inhibitors, but frequency of this event has not been comprehensively assessed. Experimental Design:We performed FISH and/or next-generation sequencing on 207 posttreatment tissue (n = 101) or plasma (n = 106) specimens from patients with ALK-positive lung cancer to detect MET genetic alterations. We...
Mon Jun 01, 2020 10:06
Purpose:Older patients with glioblastoma (GBM) are underrepresented in clinical trials. Several abbreviated and standard chemoradiotherapy regimens are advocated with no consensus on the optimal approach. Our objective was to quantitatively evaluate which of these regimens would provide the most favorable survival outcomes in older patients with GBM using a network meta-analysis. Experimental Design:MEDLINE, Embase, Google Scholar, and the Cochrane Library were searched. Patients >60 years of...
Mon Jun 01, 2020 10:06
Purpose:PARP inhibitors (PARPi) are efficacious in multiple cancers harboring germline (and possibly somatic) BRCA1/2 mutations. Acquired reversions can restore BRCA1/2 function, causing resistance to PARPi and/or platinum-based chemotherapy. The optimal method of identifying patients with germline, somatic, and/or reversion mutations in BRCA1/2 has not been established. Next-generation sequencing (NGS) of cell-free DNA (cfDNA) provides a platform to identify these three types of BRCA1/2 mutations....
Mon Jun 01, 2020 10:06
Purpose:Malignancy of cancer cells depends on the active transcription of tumor-associated genes. Recently, unique clusters of transcriptional enhancers, termed super-enhancers, have been reported to drive the expression of genes that define cell identity. In this study, we characterized specific super-enhancer–associated genes of osteosarcoma, and explored their potential therapeutic value. Experimental Design:Super-enhancer regions were characterized through chromatin immunoprecipitation sequencing...
Mon Jun 01, 2020 10:06
Purpose:Existing cell-free DNA (cfDNA) methods lack the sensitivity needed for detecting minimal residual disease (MRD) following therapy. We developed a test for tracking hundreds of patient-specific mutations to detect MRD with a 1,000-fold lower error rate than conventional sequencing. Experimental Design:We compared the sensitivity of our approach to digital droplet PCR (ddPCR) in a dilution series, then retrospectively identified two cohorts of patients who had undergone prospective plasma...
Mon Jun 01, 2020 10:06
Purpose:Patients with triple-negative breast cancer (TNBC) with homologous recombination deficient tumors achieve significantly higher pathologic complete response (pCR) rates when treated with neoadjuvant platinum-based therapy. Tumor-infiltrating lymphocytes (TIL) are prognostic and predictive of chemotherapy benefit in early stage TNBC. The relationship between TILs, BRCA1/2 mutation status, and homologous recombination deficiency (HRD) status in TNBC remains unclear. Experimental Design:We...
Mon Jun 01, 2020 10:06
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