Let-7 MicroRNA-Binding-Site Polymorphism in the 3′UTR of KRAS and Colorectal Cancer Outcome: A Systematic Review and Meta-Analysis

There is a small but growing body of literature regarding the predictive utility of a Let-7 microRNA-binding-site polymorphism in the 30 -untranslated region (UTR) of KRAS (KRAS-LCS6) for colorectal cancer outcome, although the results are conflicting. We performed a review and meta-analysis in an attempt to better clarify this relationship. A PubMed search was conducted to identify all studies reporting on KRAS let-7 microRNA-binding site polymorphism (LCS6; rs61764370) and colorectal cancer outcome. Hazard ratios (HR) and corresponding 95% confidence intervals (CI) were extracted or estimated from each manuscript. Log HRs and log CIs were combined across studies using the inverse-variance weight to calculate fixed- and random-effects summary estimates and corresponding 95% CIs for overall and progression-free survival. We did not observe any significant association between overall or progression-free survival, neither when considering all colorectal cancer patients nor for subgroup analyses (metastatic, anti-EGFR [epidermal growth factor receptor] treatment, or KRAS wild type). There was substantial heterogeneity across studies, overall and among subgroups analyzed. We have found no clear evidence to support an association between the KRAS-LCS6 genotype and overall or progression-free survival among colorectal cancer patients, even after conducting subgroup analyses by stage and anti-EGFR treatment status. This information helps to clarify the confusing body of literature regarding the clinical implications of the KRAS-LCS6 genetic variant on colorectal cancer outcomes, indicating that it should not be used at the present time to personalize therapeutic strategies (PROSPERO registration number: CRD42013005325)

MicroRNA-137 Promoter Methylation As An Etiologic and Prognostic Biomarker For Squamous Cell Carcinoma of the Head and Neck

Head and neck cancer accounted for 3.3% of incident malignancies and 2.0% of cancer-deaths in the US in 2009, the majority of which are squamous in origin. Thus, there is a need for novel biomarkers for early detection and prognosis of squamous cell carcinoma of the head and neck (SCCHN). MicroRNA-137 plays a role in cell cycle control through negative regulation of Cdk6, and has been reported to undergo promoter methylation in oral squamous cell carcinoma. Oral rinse is a non-invasive mode of DNA collection, which may have some utility in detection of promoter methylation. The primary goals of this research were to determine if miR-137 promoter methylation occurs in all SCCHN, including pharyngeal and laryngeal tumors, and whether it is detectable in oral rinse samples; and to assess miR-137 promoter methylation as an etiologic and prognostic biomarker for SCCHN. DNA was extracted from oral rinses from 99 SCCHN patients and 99 cancer-free control subjects and from tumor tissue of 67 SCCHN patients; paired oral rinses and tumor tissue was available for 64 of the SCCHN patients. Promoter methylation status of miR-137 was determined by methylation-specific PCR. We identified a strong association between miR-137 promoter methylation detected in oral rinses and SCCHN (OR = 4.80, 95% CI: 1.23-18.82). There was a strong positive association between female gender and miR-137 promoter methylation in oral rinse from SCCHN patients (OR = 5.30, 95% CI: 1.20-23.44) and an inverse association with body mass index (OR = 0.88, 95% CI: 0.77-0.99). Promoter methylation of miR-137 in tumor tissue was associated with poorer overall survival (HR = 3.68, 95% CI: 1.01-13.38). In spite of its low sensitivity (21.2%), miR-137 methylation detected in oral rinse may have future value in methylation panels for early diagnosis of SCCHN due to its high specificity (97.0%) and occurrence in early stage disease; and its detection in tumor tissue has promise as a prognostic marker. The identification of novel diagnostic and prognostic biomarkers for SCCHN such as miR-137 promoter methylation will significantly impact public health through the reduction of morbidity and mortality that occurs as a result of this disease

Disk-resolved spectral reflectance properties of Phobos from 0.3-3.2 micron: Preliminary integrated results from Phobos 2

The Phobos 2 mission provided multispectral observations of Phobos over a large wavelength range and with relatively high spectral resolution. Here, researchers integrate results from three multispectral detectors by determining the ultraviolet-visible near infrared spectral properties of color and brightness features recognized in VSK TV images. Researchers present evidence that there are two fundamental spectral units within the region of overlapping coverage by the detectors. They describe the units' spectral and reflectance properties and discuss the implications of these results for the composition of Phobos

Differential expression and prognostic value of long nonâ coding RNA in HPVâ negative head and neck squamous cell carcinoma

BackgroundLong nonâ coding RNA (lncRNA) has emerged as a new avenue of interest due to its various biological functions in cancer. Abnormal expression of lncRNA has been reported in other malignancies but has been understudied in head and neck squamous cell carcinoma (HNSCC).MethodsThe lncRNA expression was interrogated via quantitative realâ time polymerase chain reaction (qRTâ PCR) array for 19 human papillomavirus (HPV)â negative HNSCC tumorâ normal pairs. The Cancer Genome Atlas (TCGA) was used to validate these results. The association between differentially expressed lncRNA and survival outcomes was analyzed.ResultsDifferential expression was validated for 5 lncRNA (SPRY4â IT1, HEIH, LUCAT1, LINC00152, and HAND2â AS1). There was also an inverse association between MEG3 expression (not significantly differentially expressed in TCGA tumors but highly variable expression) and 3â year recurrenceâ free survival (RFS).ConclusionWe identified and validated differential expression of 5 lncRNA in HPVâ negative HNSCC. Low MEG3 expression was associated with favorable 3â year RFS, although the significance of this finding remains unclear.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144638/1/hed25136_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144638/2/hed25136.pd

In Utero Exposures, Infant Growth, and DNA Methylation of Repetitive Elements and Developmentally Related Genes in Human Placenta

BACKGROUND: Fetal programming describes the theory linking environmental conditions during embryonic and fetal development with risk of diseases later in life. Environmental insults in utero may lead to changes in epigenetic mechanisms potentially affecting fetal development. OBJECTIVES: We examined associations between in utero exposures, infant growth, and methylation of repetitive elements and gene-associated DNA in human term placenta tissue samples. METHODS: Placental tissues and associated demographic and clinical data were obtained from subjects delivering at Women and Infants Hospital in Providence, Rhode Island (USA). Methylation levels of long interspersed nuclear element-1 (LINE-1) and the Alu element AluYb8 were determined in 380 placental samples from term deliveries using bisulfite pyrosequencing. Genomewide DNA methylation profiles were obtained in a subset of 184 samples using the Illumina Infinium HumanMethylation27 BeadArray. Multiple linear regression, model-based clustering methods, and gene set enrichment analysis examined the association between birth weight percentile, demographic variables, and repetitive element methylation and gene-associated CpG locus methylation. RESULTS: LINE-1 and AluYb8 methylation levels were found to be significantly positively associated with birth weight percentile (p = 0.01 and p \u3c 0.0001, respectively) and were found to differ significantly among infants exposed to tobacco smoke and alcohol. Increased placental AluYb8 methylation was positively associated with average methylation among CpG loci found in polycomb group target genes; developmentally related transcription factor binding sites were overrepresented for differentially methylated loci associated with both elements. CONCLUSIONS: Our results suggest that repetitive element methylation markers, most notably AluYb8 methylation, may be susceptible to epigenetic alterations resulting from the intrauterine environment and play a critical role in mediating placenta function, and may ultimately inform on the developmental basis of health and disease

Recurrence in oral and pharyngeal cancer is associated with quantitative MGMT promoter methylation

<p>Abstract</p> <p>Background</p> <p>Biomarkers that predict clinical response, tumor recurrence or patient survival are severely lacking for most cancers, particularly for oral and pharyngeal cancer. This study examines whether gene-promoter methylation of tumor DNA correlates with survival and recurrence rates in a population of patients with oral or pharyngeal cancer.</p> <p>Methods</p> <p>The promoter methylation status of the DNA repair gene <it>MGMT </it>and the tumor suppressor genes <it>CDKN2A and RASSF1 </it>were evaluated by methylation-specific PCR in 88 primary oral and pharyngeal tumors and correlated with survival and tumor recurrence. Quantitative <it>MGMT </it>methylation was also assessed.</p> <p>Results</p> <p>29.6% of the tumors presented with <it>MGMT </it>methylation, 11.5% with <it>CDKN2A </it>methylation and 12.1% with <it>RASSF1 </it>methylation. <it>MGMT </it>promoter methylation was significantly associated with poorer overall and disease-free survival. No differences in methylation status of <it>MGMT </it>and <it>RASSF1 </it>with HPV infection, smoking or drinking habits were observed. A significant inverse trend with the amount of <it>MGMT </it>methylation and overall and disease-free survival was observed (p_trend= 0.002 and 0.001 respectively).</p> <p>Conclusion</p> <p>These results implicate <it>MGMT </it>promoter methylation as a possible biomarker for oral and pharyngeal cancer prognosis. The critical role of MGMT in DNA repair suggests that defective DNA repair may be correlative in the observed association between <it>MGMT </it>promoter methylation and tumor recurrence. Follow-up studies should include further quantitative MSP-PCR measurement, global methylation profiling and detailed analysis of downstream DNA repair genes regulated by promoter methylation.</p

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.

Correction to: 2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales. Archives of Virology (2021) 166:3567–3579. https://doi.org/10.1007/s00705-021-05266-wIn March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.This work was supported in part through Laulima Government Solutions, LLC prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272201800013C. J.H.K. performed this work as an employee of Tunnell Government Services (TGS), a subcontractor of Laulima Government Solutions, LLC under Contract No. HHSN272201800013C. This work was also supported in part with federal funds from the National Cancer Institute (NCI), National Institutes of Health (NIH), under Contract No. 75N91019D00024, Task Order No. 75N91019F00130 to I.C., who was supported by the Clinical Monitoring Research Program Directorate, Frederick National Lab for Cancer Research. This work was also funded in part by Contract No. HSHQDC-15-C-00064 awarded by DHS S&T for the management and operation of The National Biodefense Analysis and Countermeasures Center, a federally funded research and development center operated by the Battelle National Biodefense Institute (V.W.); and NIH contract HHSN272201000040I/HHSN27200004/D04 and grant R24AI120942 (N.V., R.B.T.). S.S. acknowledges partial support from the Special Research Initiative of Mississippi Agricultural and Forestry Experiment Station (MAFES), Mississippi State University, and the National Institute of Food and Agriculture, US Department of Agriculture, Hatch Project 1021494. Part of this work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001030), the UK Medical Research Council (FC001030), and the Wellcome Trust (FC001030).S

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly