scholarly journals A Roadmap Toward the Definition of Actionable Tumor-Specific Antigens

2020 ◽  
Vol 11 ◽  
Author(s):  
Robin Minati ◽  
Claude Perreault ◽  
Pierre Thibault

The search for tumor-specific antigens (TSAs) has considerably accelerated during the past decade due to the improvement of proteogenomic detection methods. This provides new opportunities for the development of novel antitumoral immunotherapies to mount an efficient T cell response against one or multiple types of tumors. While the identification of mutated antigens originating from coding exons has provided relatively few TSA candidates, the possibility of enlarging the repertoire of targetable TSAs by looking at antigens arising from non-canonical open reading frames opens up interesting avenues for cancer immunotherapy. In this review, we outline the potential sources of TSAs and the mechanisms responsible for their expression strictly in cancer cells. In line with the heterogeneity of cancer, we propose that discrete families of TSAs may be enriched in specific cancer types.

Reproduction ◽  
2016 ◽  
Vol 152 (6) ◽  
pp. 727-739 ◽  
Author(s):  
Andrea Miccoli ◽  
Ike Olivotto ◽  
Andrea De Felice ◽  
Iole Leonori ◽  
Oliana Carnevali

The European anchovy Engraulis encrasicolus, a member of the Clupeiformes order, holds a great biological and economical importance. In the past, this species was mostly investigated with the aim of assessing its reproductive biology, trophic ecology, population dynamics and the relations existing with the physical environment. At present days, though, an almost complete lack of information afflicts its neuroendocrinology and reproductive physiology. The hypothalamic–pituitary–gonadal (HPG) axis at its highest levels was herein investigated. In this study, the gonadotropin-releasing hormone (GnRH), a neuropeptide underlying many reproduction-related processes, the most critical of which is the stimulation of gonadotropin synthesis and secretion from the pituitary gland, was cloned. Three forms (salmon GnRH, chicken-II GnRH and the species-specific type) were characterized in their full-length open-reading frames and, in accordance with other Clupeiformes species, the distinctive one was found to be the herring-type GnRH. We qualitatively and semiquantitatively evaluated the localizations of expressions and the temporal transcription patterns of the three GnRH forms in male and female specimens throughout their reproductive cycle as well as described their phylogeny with regard to teleost GnRH lineages, and, specifically, to other Clupeiformes species.


2020 ◽  
Author(s):  
Sebastien A. Choteau ◽  
Audrey Wagner ◽  
Philippe Pierre ◽  
Lionel Spinelli ◽  
Christine Brun

ABSTRACTThe development of high-throughput technologies revealed the existence of non-canonical short open reading frames (sORFs) on most eukaryotic RNAs. They are ubiquitous genetic elements highly conserved across species and suspected to be involved in numerous cellular processes. MetamORF (http://metamorf.hb.univ-amu.fr/) aims to provide a repository of unique sORFs identified in the human and mouse genomes with both experimental and computational approaches. By gathering publicly available sORF data, normalizing it and summarizing redundant information, we were able to identify a total of 1,162,675 unique sORFs. Despite the usual characterization of ORFs as short, upstream or downstream, there is currently no clear consensus regarding the definition of these categories. Thus, the data has been reprocessed using a normalized nomenclature. MetamORF enables new analyses at loci, gene, transcript and ORF levels, that should offer the possibility to address new questions regarding sORF functions in the future. The repository is available through an user-friendly web interface, allowing easy browsing, visualization, filtering over multiple criteria and export possibilities. sORFs could be searched starting from a gene, a transcript, an ORF ID, or looking in a genome area. The database content has also been made available through track hubs at UCSC Genome Browser.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii471-iii471
Author(s):  
John Prensner ◽  
Oana Enache ◽  
Victor Luria ◽  
Karsten Krug ◽  
Karl Clauser ◽  
...  

Abstract The brain is the foremost non-gonadal tissue for expression of non-coding RNAs of unclear function. Yet, whether such transcripts are truly non-coding or rather the source of non-canonical protein translation is unknown. Here, we used functional genomic screens to establish the cellular bioactivity of non-canonical proteins located in putative non-coding RNAs or untranslated regions of protein-coding genes. We experimentally interrogated 553 open reading frames (ORFs) identified by ribosome profiling for three major phenotypes: 257 (46%) demonstrated protein translation when ectopically expressed in HEK293T cells, 401 (73%) induced gene expression changes following ectopic expression across 4 cancer cell types, and 57 (10%) induced a viability defect when the endogenous ORF was knocked out using CRISPR/Cas9 in 8 human cancer cell lines. CRISPR tiling and start codon mutagenesis indicated that the biological impact of these non-canonical ORFs required their translation as opposed to RNA-mediated effects. We functionally characterized one of these ORFs, G029442—renamed GREP1 (Glycine-Rich Extracellular Protein-1)—as a cancer-implicated gene with high expression in multiple cancer types, such as gliomas. GREP1 knockout in >200 cancer cell lines reduced cell viability in multiple cancer types, including glioblastoma, in a cell-autonomous manner and produced cell cycle arrest via single-cell RNA sequencing. Analysis of the secretome of GREP1-expressing cells showed increased abundance of the oncogenic cytokine GDF15, and GDF15 supplementation mitigated the growth inhibitory effect of GREP1 knock-out. Taken together, these experiments suggest that the non-canonical ORFeome is surprisingly rich in biologically active proteins and potential cancer therapeutic targets deserving of further study.


2020 ◽  
Author(s):  
Julie Stenberg Pedersen ◽  
Alexander Byth Carstens ◽  
Amaru Miranda Djurhuus ◽  
Witold Kot ◽  
Lars Hestbjerg Hansen

AbstractPectobacterium carotovorum is the causative agent of bacterial soft rot on various plant species. The use of phages for plant disease control have gained increased awareness over the past years. We here describe the isolation and characterization of Pectobacterium phage Jarilo, representing a novel genus of bacteriophages within the subfamily Autographivirinae. Jarilo possesses a double-stranded DNA genome of 40557 bp with a G+C% content of 50.08% and 50 predicted open reading frames (ORFs). Gene synteny and products seem to be somewhat conserved between Pectobacterium phage Jarilo and Enterobacteria phage T7, but limited nucleotide similarity is found between Jarilo and other phages within the subfamily Autographivirinae. We propose Pectobacterium phage Jarilo as the first member of a new genus of bacteriophages within the subfamily Autographivirinae.


NAR Cancer ◽  
2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Ghofran Othoum ◽  
Emily Coonrod ◽  
Sidi Zhao ◽  
Ha X Dang ◽  
Christopher A Maher

Abstract Recent studies show that annotated long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) encode for stable, functional peptides that contribute to human development and disease. To systematically discover lncRNAs and circRNAs encoding peptides, we performed a comprehensive integrative analysis of mass spectrometry-based proteomic and transcriptomic sequencing data from >900 patients across nine cancer types. This enabled us to identify 19,871 novel peptides derived from 8,903 lncRNAs. Further, we exploited open reading frames overlapping the backspliced region of circRNAs to identify 3,238 peptides that are uniquely derived from 2,834 circRNAs and not their corresponding linear RNAs. Collectively, our pan-cancer proteogenomic analysis will serve as a resource for evaluating the coding potential of lncRNAs and circRNAs that could aid future mechanistic studies exploring their function in cancer.


Author(s):  
K. T. Tokuyasu

During the past investigations of immunoferritin localization of intracellular antigens in ultrathin frozen sections, we found that the degree of negative staining required to delineate u1trastructural details was often too dense for the recognition of ferritin particles. The quality of positive staining of ultrathin frozen sections, on the other hand, has generally been far inferior to that attainable in conventional plastic embedded sections, particularly in the definition of membranes. As we discussed before, a main cause of this difficulty seemed to be the vulnerability of frozen sections to the damaging effects of air-water surface tension at the time of drying of the sections.Indeed, we found that the quality of positive staining is greatly improved when positively stained frozen sections are protected against the effects of surface tension by embedding them in thin layers of mechanically stable materials at the time of drying (unpublished).


Derrida Today ◽  
2013 ◽  
Vol 6 (1) ◽  
pp. 97-114 ◽  
Author(s):  
Christopher Morris

Over the past thirty years, academic debate over pornography in the discourses of feminism and cultural studies has foundered on questions of the performative and of the word's definition. In the polylogue of Droit de regards, pornography is defined as la mise en vente that is taking place in the act of exegesis in progress. (Wills's idiomatic English translation includes an ‘it’ that is absent in the French original). The definition in Droit de regards alludes to the word's etymology (writing by or about prostitutes) but leaves the referent of the ‘sale’ suspended. Pornography as la mise en vente boldly restates the necessary iterability of the sign and anticipates two of Derrida's late arguments: that there is no ‘the’ body and that performatives may be powerless. Deriving a definition of pornography from a truncated etymology exemplifies the prosthesis of origin and challenges other critical discourses to explain how pornography can be understood as anything more than ‘putting (it) up for sale’.


Author(s):  
Volker Scheid

This chapter explores the articulations that have emerged over the last half century between various types of holism, Chinese medicine and systems biology. Given the discipline’s historical attachments to a definition of ‘medicine’ that rather narrowly refers to biomedicine as developed in Europe and the US from the eighteenth century onwards, the medical humanities are not the most obvious starting point for such an inquiry. At the same time, they do offer one advantage over neighbouring disciplines like medical history, anthropology or science and technology studies for someone like myself, a clinician as well as a historian and anthropologist: their strong commitment to the objective of facilitating better medical practice. This promise furthermore links to the wider project of critique, which, in Max Horkheimer’s definition of the term, aims at change and emancipation in order ‘to liberate human beings from the circumstances that enslave them’. If we take the critical medical humanities as explicitly affirming this shared objective and responsibility, extending the discipline’s traditional gaze is not a burden but becomes, in fact, an obligation.


Author(s):  
K. . Togawa

Agricultural workers can be exposed to a wide variety of agents (e.g. pesticides), some of which may have adverse health effects, such as cancer. To study the health effects of agricultural exposures, an international consortium of agricultural cohort studies, AGRICOH, was established. The present analysis compared cancer incidence between the AGRICOH cohorts and the general population and found lower overall cancer incidence in the AGRICOH cohorts, with some variation across cohorts for specific cancer types. The observed lower cancer incidence may be due to healthy worker bias or lower prevalence of risk factors in the agricultural populations. Further analysis is underway.


2016 ◽  
pp. 52-65
Author(s):  
Patryk Kołodyński ◽  
Paulina Drab

Over the past several years, transplantology has become one of the fastest developing areas of medicine. The reason is, first and foremost, a significant improvement of the results of successful transplants. However, much controversy arouse among the public, on both medical and ethical grounds. The article presents the most important concepts and regulations relating to the collection and transplantation of organs and tissues in the context of the European Convention on Bioethics. It analyses the convention and its additional protocol. The article provides the definition of transplantation and distinguishes its types, taking into account the medical criteria for organ transplants. Moreover, authors explained the issue of organ donation ex vivo and ex mortuo. The European Convention on Human Rights and Biomedicine clearly regulates the legal aspects concerning the transplantation and related basic concepts, and therefore provides a reliable source of information about organ transplantation and tissue. This act is a part of the international legal order, which includes the established codification of bioethical standards.


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