Clinical utility of plasma miR‐371a‐3p in germ cell tumors

Germ cell tumours predominantly of the testis ((T)GCTs) are remarkably chemotherapy sensitive. However, a small proportion of patients fail to be cured with cisplatin‐based combination chemotherapy. miR‐371a‐3p is a new liquid biopsy biomarker for (T)GCTs. The aim of this study was to evaluate clinical utility of plasma miR‐371a‐3p level in patients starting systemic chemotherapy. Patients were included before the first cycle (N = 180) and second cycle (N = 101) of systemic first line chemotherapy, treated between July 2010 and May 2017. Plasma miR‐371a‐3p levels were measured with the ampTSmiR test and compared to disease characteristics and outcome. Pretreatment plasma miR‐371a‐3p levels were increased in 51.7% of cases and associated with number of metastatic sites, presence of lung, retroperitoneal, and mediastinal lymph node metastases, S – stage, IGCCCG risk group, and response to therapy. Patients with a negative pretreatment plasma level had better progression‐free survival (PFS) and overall survival (OS) compared to patients being positive for miR‐371a‐3p (hazard ratio [HR] = 0.26, 95% confidence interval [CI] 0.09‐0.71, P = 0.02 for PFS and HR = 0.21, 95% CI 0.07‐0.67, P = 0.03 for OS, respectively). Patients negative for miR‐371a‐3p in both samples had a superior PFS (HR = 0.10, 95% CI 0.01‐21.49, P = 0.02) and OS (HR = 0.08, 95% CI 0.01‐27.81, P = 0.008) compared to patients with miR‐371a‐3p positive in both samples (multivariate analyses were non‐significant). In total 68% of the patients were S0. This study demonstrates clinical value of plasma miR‐371a‐3p level in chemotherapy naïve (T)GCT patients starting first line of chemotherapy to predict prognosis.     

Circulating miRNA‐375 as a potential novel biomarker for active Kaposi’s sarcoma in AIDS patients

The aim of this study was to identify circulating microRNAs (miRNAs) that could be used as biomarkers in patients at risk for or affected by AIDS‐Kaposi's sarcoma (KS). Screening of 377 miRNAs was performed using low‐density arrays in pooled plasma samples of 10 HIV/human herpesvirus 8 (HHV8)‐infected asymptomatic and 10 AIDS‐KS patients before and after successful combined antiretroviral therapy (cART). MiR‐375 was identified as a potential marker of active KS, being the most down‐regulated in AIDS‐KS patients after cART and the most up‐regulated in naïve AIDS‐KS patients compared to naïve asymptomatic subjects. Validation on individual plasma samples confirmed that miR‐375 levels were higher in AIDS‐KS compared to asymptomatic patients, decreased after cART‐induced remission in most AIDS‐KS patients and increased in patients with active KS. In asymptomatic patients miR‐375 was up‐regulated after cART in both screening and validation. Statistical analyses revealed an association between miR‐375 changes and CD4 cell counts, which could explain the discordant cases and the opposite trend between asymptomatic and AIDS‐KS patients. These data suggest that circulating miR‐375 might be a good indicator of active AIDS‐KS. Moreover, changes in miR‐375 levels may have a prognostic value in HIV/HHV8‐infected patients undergoing treatment. Further large‐scale validation is needed.     

Drug resistance‐related microRNAs in osteosarcoma: Translating basic evidence into therapeutic strategies

Although the application of multiple chemotherapy brought revolutionary changes to improve overall survival of osteosarcoma patients, the existence of multidrug resistance (MDR) has become a great challenge for successful osteosarcoma treatment in recent decades. Substantial studies have revealed various underlying mechanisms of MDR in cancers. As for osteosarcoma, evidence has highlighted that microRNAs (miRNAs) can mediate in the processes of DNA damage response, apoptosis avoidance, autophagy induction, activation of cancer stem cells, and signal transduction. Besides, these drug resistance‐related miRNAs showed much promise for serving as candidates for predictive biomarkers of poor outcomes and shorter survival time, and therapeutic targets to reverse drug resistance and overcome treatment refractoriness. This review aims to demonstrate the potential molecular mechanisms of miRNAs‐regulated drug resistance in osteosarcoma, and provide insight in translating basic evidence into therapeutic strategies.     

New insight into the role of extracellular vesicles in kidney disease

Extracellular vesicles (EVs) are released to maintain cellular homeostasis as well as to mediate cell communication by spreading protective or injury signals to neighbour or remote cells. In kidney, increasing evidence support that EVs are signalling vesicles for different segments of tubules, intra‐glomerular, glomerular‐tubule and tubule‐interstitial communication. EVs released by kidney resident and infiltrating cells can be isolated from urine and were found to be promising biomarkers for kidney disease, reflecting deterioration of renal function and histological change. We have here summarized the recent progress about the functional role of EVs in kidney disease as well as challenges and future directions involved.     

An electrochemical biosensor for prostate cancer biomarker detection using graphene oxide–gold nanostructures

In this paper, a most sensitive electrochemical biosensor for detection of prostate‐specific antigen (PSA) was designed. To reach the goal, a sandwich type electrode composed of reduced graphene oxide/ gold nanoparticles (GO/AuNPs), Anti‐Total PSA monoclonal antibody, and anti‐Free PSA antibody was assembled. The functionalized materials were thoroughly characterized by atomic force microscope spectroscopy, transmission electron microscopy, and X‐ray diffraction techniques. The electrochemical properties of each of the modification step were evaluated by cyclic voltammetry and electrochemical impedance spectroscopy. The results presented that the proposed biosensor possesses high sensitivity toward total and free PSA. Furthermore, the fabricated biosensor revealed an excellent selectivity for PSA in comparison to the other tumor markers such as BHCG, Alb, CEA, CA125, and CA19‐9. The limit of detection for the proposed electrochemical biosensor was estimated to be around 0.2 and 0.07 ng/mL for total and free PSA antigen, respectively.     

Levels of IL-17F and IL-33 correlate with HLA-DR activation in clinical-grade human bone marrow–derived multipotent mesenchymal stromal cell expansion cultures

Background aims

Multipotent mesenchymal stromal cell (MSC)-based medicines are extensively investigated for use in regenerative medicine and immunotherapy applications. The International Society for Cell and Gene Therapy (ISCT) proposed a panel of cell surface molecules for MSC identification that includes human leukocyte antigen (HLA)-DR as a negative marker. However, its expression is largely unpredictable despite production under tightly controlled conditions and compliance with current Good Manufacturing Practices. Herein, we report the frequency of HLA-DR expression in 81 batches of clinical grade bone marrow (BM)-derived MSCs and investigated its impact on cell attributes and culture environment.

Environmental controls on bacteriohopanepolyol profiles of benthic microbial mats from Lake Fryxell,Antarctica

Bacteriohopanepolyols (BHPs) are pentacyclic triterpenoid lipids that contribute to the structural integrity and physiology of some bacteria. Because some BHPs originate from specific classes of bacteria, BHPs have potential as taxonomically and environmentally diagnostic biomarkers. For example, a stereoisomer of bacteriohopanetetrol (informally BHT II) has been associated with anaerobic ammonium oxidation (anammox) bacteria and suboxic to anoxic marine environments where anammox is active. As a result, the detection of BHT II in the sedimentary record and fluctuations in the relative abundance of BHT II may inform reconstructions of nitrogen cycling and ocean redox changes through the geological record. However, there are uncertainties concerning the sources of BHT II and whether or not BHT II is produced in abundance in non‐marine environments, both of which are pertinent to interpretations of BHT II signatures in sediments. To address these questions, we investigate the BHP composition of benthic microbial mats from Lake Fryxell, Antarctica. Lake Fryxell is a perennially ice‐covered lake with a sharp oxycline in a density‐stabilized water column. We describe the diversity and abundance of BHPs in benthic microbial mats across a transect from oxic to anoxic conditions. Generally, BHP abundances and diversity vary with the morphologies of microbial mats, which were previously shown to reflect local environmental conditions, such as irradiance and oxygen and sulfide concentrations. BHT II was identified in mats that exist within oxic to anoxic portions of the lake. However, anammox bacteria have yet to be identified in Lake Fryxell. We examine our results in the context of BHPs as biomarkers in modern and ancient environments.     

Cancer biomarker discovery and translation: proteomics and beyond

Introduction: Cancer is often diagnosed at late stages when the chance of cure is relatively low and although research initiatives in oncology discover many potential cancer biomarkers, few transition to clinical applications. This review addresses the current landscape of cancer biomarker discovery and translation with a focus on proteomics and beyond.

Areas covered: The review examines proteomic and genomic techniques for cancer biomarker detection and outlines advantages and challenges of integrating multiple omics approaches to achieve optimal sensitivity and address tumor heterogeneity. This discussion is based on a systematic literature review and direct participation in translational studies.

Expert commentary: Identifying aggressive cancers early on requires improved sensitivity and implementation of biomarkers representative of tumor heterogeneity. During the last decade of genomic and proteomic research, significant advancements have been made in next generation sequencing and mass spectrometry techniques. This in turn has led to a dramatic increase in identification of potential genomic and proteomic cancer biomarkers. However, limited successes have been shown with translation of these discoveries into clinical practice. We believe that the integration of these omics approaches is the most promising molecular tool for comprehensive cancer evaluation, early detection and transition to Precision Medicine in oncology.     

Domain-specific Quantification of Prion Protein in Cerebrospinal Fluid by Targeted Mass Spectrometry

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Highlights

• •Targeted mass spectrometry assay to quantify prion protein (PrP) in spinal fluid.
• •Precise measurement of PrP peptide concentration across protein domains.
• •Peptides are uniformly decreased in symptomatic prion disease patients.
• •Assay applicable to humans and preclinical species for drug development.