3 research outputs found
Trimodality treatment in gastric and gastroesophageal junction cancers: Current approach and future perspectives
No full textGastric and gastroesophageal junction (GEJ) cancers represent an aggressive group of malignancies with poor prognosis even when diagnosed in relatively early stage, with an increasing incidence both in Asia and in Western countries. These cancers are characterized by heterogeneity as a result of different pathogenetic mechanisms as shown in recent molecular analyses. Accordingly, the understanding of phenotypic and genotypic correlations/classifications has been improved. Current therapeutic strategies have also advanced and moved beyond surgical extirpation alone, with the incorporation of other treatment modalities, such as radiation and chemotherapy (including biologics). Chemoradiotherapy has been used as postoperative treatment after suboptimal gastrectomy to ensure local disease control but also improvement in survival. Preoperative chemoradiotherapy/chemotherapy has been employed to increase the chance of a successful R0 resection and pathologic complete response rate, which is associated with improved long-term outcomes. Several studies have defined various chemotherapy regimens to accompany radiation (before and after surgery). Recently, addition of immunotherapy after trimodality of gastroesophageal cancer has produced an advantage in disease-free interval. Targeted agents used in the metastatic setting are being investigated in the early setting with mixed results. The aim of this review is to summarize the existing data on trimodality approaches for gastric and GEJ cancers, highlight the remaining questions and present the current research effort addressing them. © 2022. The Author(s). Published by Baishideng Publishing Group Inc. All Rights Reserved
Telomere-to-telomere genome assembly of Microsporidia sp. MB, a microsporidian symbiont of Anopheles coluzzii isolated from Burkina Faso
No full textBackground: Microsporidia sp. MB is an intracellular parasite of anopheline mosquitoes identified across the African continent. Microsporidia sp. MB infections appear to have no significant effect
on host fitness and vertically transmit, whilst infected individuals have exhibited significantly
reduced levels of Plasmodium falciparum transmission. These combined characteristics make
Microsporidia sp. MB a promising candidate for use in malaria control. A comprehensive genome would greatly facilitate investigation into the evolution and biological pathways underlying
important phenotypes, such as the mechanism of malarial inhibition.
Results:
In this study, we present the de novo assembly of the first complete genome of
Microsporidia sp. MB SOUVK7. Multi-platform sequencing was performed on ovary samples of
laboratory established Anopheles coluzzii collected from Burkina Faso. The SOUVK7 genome
has a total size of 9.16Mb, encodes 2,435 genes and is organised into 13 chromosomes with
telomeres identified at all flanks. Telomeric repeats exhibit a 4-mer motif due to a glutamine
deletion previously unobserved in Microsporidia. Ploidy analysis of Illumina reads predicts MB
as tetraploid, whilst analysis of CpG methylation and retroelements highlights loci in all
chromosomes with characteristics consistent with regional centromeres. Orthology analysis
identifies several key genes in pathways associated to telomeric and centromeric maintenance,
along with methylation and host invasion machinery. A loss of several components of the
infection machinery is observed in Microsporidia sp. MB and the wider Enterocytozoonida,
consistent with a general trend towards genome size reduction in the clade.
Conclusion:
This study provides the first complete, telomere to telomere assembly of Microsporidia
sp. MB, offering new insight into the genomic architecture of Microsporidia sp. MB and the
broader Mrazekiidae family
Imaging the lifecycle of Microsporidia sp. MB in Anopheles coluzzii from western Burkina Faso reveals octosporogony
No full textA newly discovered microsporidian, Microsporidia sp. MB (MB), was recently found to block Plasmodium falciparum transmission in Anopheles arabiensis mosquitoes from Kenya. Here, we describe the lifecycle of the first laboratory colony of Anopheles coluzzii with MB, originating from western Burkina Faso. The lifecycle of MB was explored using fluorescent in situ hybridization and confocal microscopy, facilitated by the development of optimized protocols to produce histological sections of whole adult, larval, and embryo tissues. As in An. arabiensis, transmission appears to be predominantly vertical, with MB highly localized to the ovaries across multiple lifecycle stages. MB was sparsely distributed within the majority of developing oocytes in the gravid female. After oviposition, in the majority of embryos, MB relocated to the developing gonad at the onset of tissue differentiation, suggesting a highly specialized adaptation to host tissues. Sporogony was identified for the first time in a proportion of developing oocytes and in embryos post-oviposition. Microsporidian spore characteristics were subsequently confirmed with electron microscopy. Identification of MB sporogony in eggs suggests there are alternative horizontal routes of transmission which could play an important role in developing MB as a malaria control strategy
