- Nanoengineered Metasurface Immunosensor with over 1000-Fold Electrochemiluminescence Enhancement for Ultra-sensitive Bioassay. [Journal Article]
- IiScience 2019 Jul 03; 17:267-276
- Enhancing electrochemiluminescence (ECL) with plasmonic materials is promising but still a long-standing barrier to improve its sensitivity for ultrasensitive bioassays, due to the lack of comprehens…
Enhancing electrochemiluminescence (ECL) with plasmonic materials is promising but still a long-standing barrier to improve its sensitivity for ultrasensitive bioassays, due to the lack of comprehensive understanding and effective strategies to fully utilize plasmonic effects for ECL enhancement. Herein, by insulating gold nanoparticles with silica shells (Au@SiO2 NPs), and finely tuning their core/shell sizes and controlling interparticle spacing via assembling them into a dense nanomembrane, we develop a novel 2D metasurface. Due to well-controlled high density "hot spots" and 2D ordered arrangement of the unit NPs in the nanomembrane, the metasurfaced ECL electrode shows over 1,000-fold plasmonic ECL enhancement for the classical Ru(bpy)32+-tripropylamine system, which is two orders of magnitude higher than ever reported (<30-fold). Such fabricated ECL biosensor demonstrates superior detection performance for prostate-specific antigen with a detection limit of 3 fg mL-1. Our results provide understanding of plasmonic effects for ECL enhancement and will benefit for biosensor construction for ultrasensitive bioassays.
- Emerging role of vitamin D in autoimmune diseases: An update on evidence and therapeutic implications. [Review]
- ARAutoimmun Rev 2019 Jul 16; :102350
- Vitamin D plays a key role in in calcium homeostasis and, thus, provides an important support in bone growth by aiding in the mineralization of the collagen matrix. However, vitamin D performs variou…
Vitamin D plays a key role in in calcium homeostasis and, thus, provides an important support in bone growth by aiding in the mineralization of the collagen matrix. However, vitamin D performs various immunomodulatory, anti-inflammatory, antioxidant and anti-fibrotic actions. Autoimmune diseases result from an aberrant activation of the immune system, whereby the immune response is directed against harmless self-antigens. Does vitamin D play a role in the pathophysiology of autoimmune diseases? And, if so, what is its role? In the last decade, researchers' interest in vitamin D and its correlations with autoimmune diseases has considerably increased. We conducted a literature review, covering the period January 1, 2009 through March 30, 2019, in PubMed. We analyzed more than 130 studies in order to find a correlation between vitamin D levels and its effect upon several autoimmune diseases. The analysis demonstrated an inverse association between vitamin D and the development of several autoimmune diseases, such as SLE, thyrotoxicosis, type 1 DM, MS, iridocyclitis, Crohn's disease, ulcerative colitis, psoriasis vulgaris, seropositive RA, polymyalgia rheumatica. International multicenter study could allow us to confirm the data already present in the literature in the single clinical studies and to evaluate when to effectively supplement vitamin D in patients who do not take corticosteroids.
- Antiphospholipid syndrome's genetic and epigenetic aspects. [Review]
- ARAutoimmun Rev 2019 Jul 16; :102352
- Studies on last genetic and epigenetic predisposition to APS are summarized. It is well known that genetic predisposition is in HLA system (DR4 and DRw53) and that lupus anticoagulant (LA) and antica…
Studies on last genetic and epigenetic predisposition to APS are summarized. It is well known that genetic predisposition is in HLA system (DR4 and DRw53) and that lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) are both associated with the same HLA antigens. Other genes, outside the MHC, give their contribution to the development of this autoimmune syndrome, such as IRF5, STAT4 and those related to inherited thrombophilia - factor V Leiden and G20210A prothrombin polymorphisms. Finally, post-transcriptional modifications of anti-beta2GPI antibodies could be implicated too. The most important discovery of last years is that altered microRNAs' expression is linked to autoimmunity, thrombosis, early atherosclerosis, and oxidative stress in APS.
- Pembrolizumab for the treatment of Cervical Cancer. [Journal Article]
- EOExpert Opin Biol Ther 2019 Jul 19
- Introduction The prognosis of patients with recurrent and/or metastatic cervical cancer remains poor, with a 5-year survival rate of 17%. Most of cervical cancers are associated with the human papill…
Introduction The prognosis of patients with recurrent and/or metastatic cervical cancer remains poor, with a 5-year survival rate of 17%. Most of cervical cancers are associated with the human papillomavirus (HPV) infection that leads to viral antigens production, supporting the development of immunotherapy in cervical cancer. Areas covered Here we report the pharmacologic properties, clinical efficacy, and safety profile of pembrolizumab, an IgG4-kappa humanized monoclonal antibody against the programmed cell death protein 1 (PD-1) receptor, for the treatment of cervical cancer. Expert Opinion Single agent pembrolizumab has limited efficacy in the recurrent and/or metastatic setting in an unselected patient population. However, durable responses in PD-L1-expressing cervical cancer patients led the U.S. Food and Drug Administration to grant accelerated approval of pembrolizumab in this patient population. Outside this patient population, further development involves combinations with other treatment options including chemotherapy, radiotherapy and other immunotherapeutic agents. The identification of biomarkers of efficacy beyond PD-L1 expression will be essential in order to identify patients who will most likely benefit from pembrolizumab.
- Impact of circulating tumor DNA mutant allele fraction on prognosis in RAS-mutant metastatic colorectal cancer. [Journal Article]
- MOMol Oncol 2019 Jul 19
- Despite major advances in the treatment of metastatic colorectal cancer (mCRC), the survival rate remains very poor. This study aims at exploring the prognostic value of RAS mutant allele fraction (M…
Despite major advances in the treatment of metastatic colorectal cancer (mCRC), the survival rate remains very poor. This study aims at exploring the prognostic value of RAS mutant allele fraction (MAF) in plasma in mCRC. Forty-seven plasma samples from 37 RAS-mutated patients with non-resectable metastases were tested for RAS in circulating tumor DNA (ctDNA) using BEAMing before first and/or second-line treatment. RAS MAF was correlated with several clinical parameters (number of metastatic sites, hepatic volume, carcinoembryonic antigen, CA19-9 levels, primary site location and treatment line) and clinical outcome (PFS and OS). An independent cohort of 32 patients from the CAPRI-GOIM trial was assessed for clinical outcome based on plasma baseline MAF. RAS MAF analysis at baseline revealed a significant correlation with longer OS (HR=3.514; P=0.00066). Patients with lower MAF also showed a tendency to longer PFS, although not statistically significant. Multivariate analysis showed RAS MAFs as an independent prognostic factor in both OS (HR=2.73; P=0.006) and first-line PFS (HR=3.74; P=0.049). Tumor response to treatment in patients with higher MAF was progression disease (P=0.007). Patients with low MAFs at baseline in the CAPRI-GOIM group also showed better OS (HR=3.84; 95% CI 1.5 - 9.6; P=0.004) and better PFS (HR=2.5; 95% CI 1.07 - 5.62; P=0.033). This minimally invasive test may help in adding an independent factor to better estimate outcomes before initiating treatment. Further prospective studies using MAF as a stratification factor could further validate its utility in clinical practice.
- Growth inhibition and transcriptional effects of ribavirin in lymphoma. [Journal Article]
- OROncol Rep 2019 Jul 17
- Ribavirin exhibits inhibitory effects on the epigenetic enzyme enhancer of zeste homolog 2 (EZH2), which participates in lymphomagenesis. Additionally, preclinical and clinical studies have demonstra…
Ribavirin exhibits inhibitory effects on the epigenetic enzyme enhancer of zeste homolog 2 (EZH2), which participates in lymphomagenesis. Additionally, preclinical and clinical studies have demonstrated the anti‑lymphoma activity of this drug. To further investigate the potential of ribavirin as an anticancer treatment for lymphoma, the tumor‑suppressive effects of ribavirin were analyzed in lymphoma cell lines. The effects of ribavirin on the viability and clonogenicity of the B‑cell lymphoma cell line Pfeiffer (EZH2‑mutant), Toledo (EZH2 wild‑type) and cutaneous T‑cell lymphoma Hut78 cell line were assessed. Expression of EZH2 and trimethylation status of histone 3, lysine 27 trimethylated (H3K27m3) was also determined in response to ribavirin. The transcriptional effects of ribavirin on Hut78 cells were analyzed by microarray expression and the results were validated by reverse transcription‑quantitative polymerase chain reaction, western blotting and knockout of signal transducer and activator of transcription 1 (STAT1). The results of the present study demonstrated that ribavirin suppressed the growth and clonogenicity of cells in a dose‑dependent manner. Ribavirin did not affect the expression of EZH2 nor altered its activity as evaluated by H3K27 trimethylation status. Furthermore, the results of transcriptome analysis indicated that the majority of the canonical pathways affected by ribavirin were associated with the immune system, including 'antigen presentation', 'communication between innate and adaptive immune cells' and 'cross‑talk between dendritic and natural killer cells'. The results of gene expression analysis were confirmed, by demonstrating at the RNA and protein levels, downregulation of stearoyl‑CoA desaturase and upregulation of STAT1. Depletion of STAT1, which was proposed as a key regulator of the aforementioned pathways, exerted growth inhibitory effects almost to the same extent as ribavirin. In conclusion, ribavirin was proposed to exert growth inhibitory effects on lymphoma cell lines, particularly Hut78 cells, a cutaneous T‑cell lymphoma cell line. Of note, these effects may depend on, at least in part, the activation of canonical immune pathways regulated by the key factors STAT1 and interferon‑γ. Our results provide insight into the anti‑lymphoma potential of ribavirin; however, further investigations in preclinical and clinical studies are required to determine the effectiveness of ribavirin as a therapeutic agent for treating lymphoma.
- HLA-DQB1*03:01:01:21Q, a novel HLA-DQB1 allele, detected in a Spanish volunteer bone marrow donor. [Journal Article]
- HLAHLA 2019 Jul 18
- HLA-DQB1*03:01:01:21Q differs from HLA-DQB1*03:01:01:03 by a single-nucleotide substitution (G → A) at position 1 of intron 3. This article is protected by copyright. All rights reserved.
HLA-DQB1*03:01:01:21Q differs from HLA-DQB1*03:01:01:03 by a single-nucleotide substitution (G → A) at position 1 of intron 3. This article is protected by copyright. All rights reserved.
- Durvalumab With or Without Tremelimumab for Patients With Metastatic Pancreatic Ductal Adenocarcinoma: A Phase 2 Randomized Clinical Trial. [Journal Article]
- JOJAMA Oncol 2019 Jul 18
- CONCLUSIONS: Treatment was well tolerated, and the efficacy of durvalumab plus tremelimumab therapy and durvalumab monotherapy reflected a population of patients with mPDAC who had poor prognoses and rapidly progressing disease. Patients were not enrolled in part B because the threshold for efficacy was not met in part A.
- Opt-out bloodborne virus screening: a cross-sectional observational study in an acute medical unit. [Journal Article]
- BOBMJ Open 2019 Jul 16; 9(7):e022777
- CONCLUSIONS: BBV testing uptake of 40.4% is higher than previous studies in AMU settings that used opt-in strategies, but lower than expected, possibly due to not incorporating testing into routine practice. The diagnosed prevalence of HBV is notable as little data currently exist about its prevalence in Ireland. These data are valuable in order to inform further prevention strategies for these infections in low-prevalence settings.
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- Comprehensive Immune Monitoring of Clinical Trials to Advance Human Immunotherapy. [Journal Article]
- CRCell Rep 2019 Jul 16; 28(3):819-831.e4
- The success of immunotherapy has led to a myriad of clinical trials accompanied by efforts to gain mechanistic insight and identify predictive signatures for personalization. However, many immune mon…
The success of immunotherapy has led to a myriad of clinical trials accompanied by efforts to gain mechanistic insight and identify predictive signatures for personalization. However, many immune monitoring technologies face investigator bias, missing unanticipated cellular responses in limited clinical material. We present here a mass cytometry (CyTOF) workflow for standardized, systems-level biomarker discovery in immunotherapy trials. To broadly enumerate immune cell identity and activity, we established and extensively assessed a reference panel of 33 antibodies to cover major cell subsets, simultaneously quantifying activation and immune checkpoint molecules in a single assay. This assay enumerates ≥98% of peripheral immune cells with ≥4 positively identifying antigens. Robustness and reproducibility are demonstrated on multiple samples types, across two research centers and by orthogonal measurements. Using automated analysis, we identify stratifying immune signatures in bone marrow transplantation-associated graft-versus-host disease. Together, this validated workflow ensures comprehensive immunophenotypic analysis and data comparability and will accelerate biomarker discovery.