Exosomes in Inflammation and Inflammatory Disease Chan, Brandon Dow; Wong, Wing‐Yan; Lee, Magnolia Muk‐Lan ...
Proteomics (Weinheim),
April 2019, 2019-04-00, 20190401, Letnik:
19, Številka:
8
Journal Article
Recenzirano
Exosomes are a subset of extracellular vesicles released by all cell types and involved in local and systemic intercellular communication. In the past decade, research into exosomes has swelled as ...their important role in the mediation of health and disease has been increasingly established and acknowledged. Exosomes carry a diverse range of cargo including proteins, nucleic acids, and lipids derived from their parental cell that, when delivered to the recipient cell, can confer pathogenic or therapeutic effects through modulation of immunity and inflammation. In this review, the role of exosomes on mediation of immune and inflammatory responses, and their participation in diseases with a significant inflammatory component is discussed. The considerable potential for exosomes in therapy and diagnosis of inflammatory diseases is also highlighted.
The role of miR‐34 in cancer drug resistance Naghizadeh, Sanaz; Mohammadi, Ali; Duijf, Pascal H. G. ...
Journal of cellular physiology,
October 2020, 2020-10-00, 20201001, Letnik:
235, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Resistance to conventional chemotherapy remains a major cause of cancer relapse and cancer‐related deaths. Therefore, there is an urgent need to overcome resistance barriers. To improve cancer ...treatment approaches, it is critical to elucidate the basic mechanisms underlying drug resistance. Increasingly, the mechanisms involving micro‐RNAs (miRNAs) are studied because miRNAs are also considered practical therapeutic options due to high degrees of specificity, efficacy, and accuracy, as well as their ability to target multiple genes at the same time. Years of research have firmly established miR‐34 as a key tumor suppressor miRNA whose target genes are involved in drug resistance mechanisms. Indeed, numerous articles show that low levels of circulating miR‐34 or tumor‐specific miR‐34 expression are associated with poor response to chemotherapy. In addition, elevation of inherently low miR‐34 levels in resistant cancer cells effectively restores sensitivity to chemotherapeutic agents. Here, we review this literature, also highlighting some contradictory observations. In addition, we discuss the potential utility of miR‐34 expression as a predictive biomarker for chemotherapeutic drug response. Although caution needs to be exercised, miR‐34 is emerging as a biomarker that could improve cancer precision medicine.
This review article aims to provide an extensive overview and discuss the achievements of this study, highlighting the combination of therapies involving miR‐34a and diverse chemotherapeutics agents to treat several types of cancer.
Cell free RNA (cfRNA) contains transcript fragments from multiple cell types, making it useful for cancer detection in clinical settings. However, the pathophysiological origins of cfRNAs in plasma ...from colorectal cancer (CRC) patients remain unclear.
To identify the tissue-specific contributions of cfRNAs transcriptomic profile, we used a published single-cell transcriptomics profile to deconvolute cell type abundance among paired plasma samples from CRC patients who underwent tumor-ablative surgery. We further validated the differentially expressed cfRNAs in 5 pairs of CRC tumor samples and adjacent tissue samples as well as 3 additional CRC tumor samples using RNA-sequencing.
The transcriptomic component from intestinal secretory cells was significantly decreased in the in-house post-surgical cfRNA. The
,
, and
expression was consistent across cfRNA and tissue samples. Using the Cancer Genome Atlas (TCGA) CRC datasets, we were able to classify the patients into two groups with significantly different survival outcomes.
The three-gene signature holds promise in applying minimal residual disease (MRD) testing, which involves profiling remnants of cancer cells after or during treatment. Biomarkers identified in the present study need to be validated in a larger cohort of samples in order to ascertain their possible use in early diagnosis of CRC.
Using Epstein‐Barr virus (EBV)‐induced cancer cells and HeLa cells as a comparative study model, a novel and safe dual‐EBV‐oncoproteins‐targeting pH‐responsive peptide engineering, coating, and ...guiding approach to achieve precision targeting and treatment strategy against EBV‐associated cancers is introduced. Individual functional peptide sequences that specifically bind to two overexpressed EBV‐specific oncoproteins, EBNA1 (a latent cellular protein) and LMP1 (a transmembrane protein), are engineered in three different ways and incorporated with a pH‐sensitive tumor microenvironment (TME)‐cleavable linker onto the upconversion nanoparticles (UCNP) NaGdF4:Yb3+, Er3+@NaGdF4 (UCNP‐Pn, n = 5, 6, and 7). A synergistic combination of the transmembrane LMP1 targeting ability and the pH responsiveness of UCNP‐Pn is found to give specific cancer differentiation with higher cellular uptake and accumulation in EBV‐infected cells, thus a lower dose is needed and the side effects and health risks from treatment would be greatly reduced. It also gives responsive UC signal enhancement upon targeted dual‐protein binding and shows efficacious EBV cancer inhibition in vitro and in vivo. This is the first example of simultaneous imaging and inhibition of two EBV latent proteins, and serves as a blueprint for next‐generation peptide‐guided precision delivery nanosystem for the safe monitoring and treatment against one specific cancer.
The upconversion nanoplatform with desired responsiveness toward tumor microenvironment is introduced. Thereafter, EBV‐cancer model is used to investigate by utilizing the safe nanoplatform via targeting LMP1 and EBNA1 with responsive emission, satisfactory prohibitive performances are observed in vitro and in vivo, thanks to the specific dual‐targeting peptides. This proposed multifunctional nanoplatform can achieve both monitoring and treatment for EBV cancer.
In the development of the skeleton, the long bones are arising from the process of endochondral ossification (EO) in which cartilage is replaced by bone. This complex process is regulated by various ...factors including genetic, epigenetic, and environmental elements. It is recognized that DNA methylation, higher-order chromatin structure, and post-translational modifications of histones regulate the EO. With emerging understanding, non-coding RNAs (ncRNAs) have been identified as another mode of EO regulation, which is consist of microRNAs (miRNAs or miRs) and long non-coding RNAs (lncRNAs). There is expanding experimental evidence to unlock the role of ncRNAs in the differentiation of cartilage cells, as well as the pathogenesis of several skeletal disorders including osteoarthritis. Cutting-edge technologies such as epigenome-wide association studies have been employed to reveal disease-specific patterns regarding ncRNAs. This opens a new avenue of our understanding of skeletal cell biology, and may also identify potential epigenetic-based biomarkers. In this review, we provide an updated overview of recent advances in the role of ncRNAs especially focus on miRNA and lncRNA in the development of bone from cartilage, as well as their roles in skeletal pathophysiology.
Colorectal cancer (CRC) threatens human health seriously. Early diagnosis of CRC is critical to improving patient survival. Meanwhile, non-invasive detection through tumor-circulating markers can be ...an important auxiliary diagnosis. In this study, we performed targeted RNA sequencing in paired tumor and adjacent normal fresh frozen tissues from 68 patients, and we also measured circulating mRNA levels in 4 time-point plasma samples collected before and after operation or chemotherapy. Our results showed that
SOX9
(6.73-fold with adjusted
p
value < 1 × 10
–45
),
MYC
(20.59-fold with adjusted
p
value < 1 × 10
–57
), and
MMP7
(131.94-fold with adjusted
p
value < 1 × 10
–78
) highly expressed in tumor compared with adjacent normal tissues. Besides, the circulating mRNA of
SOX9
(41.14-fold with adjusted
p
value < 1 × 10
–13
) in CRC was significantly higher than in the normal control as well. Moreover, a
SOX9
-based 9-gene panel (
SOX9
,
GSK3A
,
FZD4
,
LEF1
,
DVL1
,
FZD7
,
NFATC1
,
KRT19
, and
RUVBL1
) showed the non-invasive diagnostic value of CRC (AUC: 0.863 (0.766–0.960), TPR: 0.92, TNR: 0.87). In summary,
SOX9
expression consistently increases in tumor and plasma samples from CRC patients, which indicates the important role of
SOX9
in CRC progression and its potential in non-invasive diagnosis of CRC.
Inflammatory bowel disease (IBD) is an idiopathic inflammatory disease affecting the gastrointestinal tract. IBD is characterized by courses of relapse and remission, and remains incurable. Although ...multiple factors are related to the pathogenesis of IBD, disruption of intestinal mucosa homeostasis has been proposed to be a major contributor to IBD, and abnormal activation of immune cells is key for initiation of the inflammatory response. Macrophages are the most abundant immune cells in the intestine. Once activated, they are responsible for secretion of pro-inflammatory cytokines and chemokines to attract circulating monocytes to inflammatory sites, exacerbating the inflammatory response, and leading to tissue damage. Therefore, the suppression of activated macrophages, cytokine/chemokine production, and subsequent monocyte chemotaxis possesses great potential for the treatment of IBD. In our study, we have demonstrated the inhibitory effect of
Centipeda minima
total extract (CME) on the activation of NF-κB, STAT3, and MAPK signaling in LPS-stimulated RAW264.7 macrophages. In addition, we identified the significant suppressive effect of CME on CCL8 expression in activated macrophages, which potentially contributed to inhibition of monocyte chemotaxis. In the DSS-induced acute colitis mouse model, we have demonstrated the suppressive effect of CME on intestinal macrophage infiltration and its ameliorative effect in IBD. Altogether, we have provided evidence of the therapeutic effect of CME in IBD and the potential of CME for the treatment of IBD.
Circulating tumor RNA (ctRNA) has recently emerged as a novel and attractive liquid biomarker. CtRNA is capable of providing important information about the expression of a variety of target genes ...noninvasively, without the need for biopsies, through the use of circulating RNA sequencing. The overexpression of cancer-specific transcripts increases the tumor-derived RNA signal, which overcomes limitations due to low quantities of circulating tumor DNA (ctDNA). The purpose of this work is to present an up-to-date review of current knowledge regarding ctRNAs and their status as biomarkers to address the diagnosis, prognosis, prediction, and drug resistance of colorectal cancer. The final section of the article discusses the practical aspects involved in analyzing plasma ctRNA, including storage and isolation, detection technologies, and their limitations in clinical applications.
Nasopharyngeal carcinoma (NPC) is a rare malignancy in most part of the world and it is one of the most confusing, commonly misdiagnosed and poorly understood diseases. The cancer is an Epstein-Barr ...virus-associated malignancy with a remarkable racial and geographical distribution. It is highly prevalent in southern Asia where the disease occurs at a prevalence about a 100-fold higher compared with other populations not at risk. The etiology of NPC is thought to be associated with a complex interaction of genetic, viral, environmental and dietary factors. Thanks to the advancements in genomics, proteomics and bioinformatics in recent decades, more understanding of the disease etiology, carcinogenesis and progression has been gained. Research into these components may unravel the pathways in NPC development and potentially decipher the molecular characteristics of the malignancy. In the era of molecular medicine, specific treatment to the potential target using technologies such as immunotherapy and RNAi becomes formulating from bench to bedside application and thus makes molecular biomarker discovery more meaningful for NPC management. In this article, the latest molecular biomarker discovery and progress in NPC is reviewed with respect to the diagnosis, monitoring, treatment and prognostication of the disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The combination of a PD-L1 inhibitor and an anti-angiogenic agent has become the new reference standard in the first-line treatment of non-excisable hepatocellular carcinoma (HCC) due to the survival ...advantage, but its objective response rate remains low at 36%. Evidence shows that PD-L1 inhibitor resistance is attributed to hypoxic tumor microenvironment. In this study, we performed bioinformatics analysis to identify genes and the underlying mechanisms that improve the efficacy of PD-L1 inhibition. Two public datasets of gene expression profiles, (1) HCC tumor versus adjacent normal tissue (
= 214) and (2) normoxia versus anoxia of HepG2 cells (
= 6), were collected from Gene Expression Omnibus (GEO) database. We identified HCC-signature and hypoxia-related genes, using differential expression analysis, and their 52 overlapping genes. Of these 52 genes, 14 PD-L1 regulator genes were further identified through the multiple regression analysis of TCGA-LIHC dataset (
= 371), and 10 hub genes were indicated in the protein-protein interaction (PPI) network. It was found that
,
,
,
, and
play critical roles in the response and overall survival in cancer patients under PD-L1 inhibitor treatment. Our study provides new insights and potential biomarkers to enhance the immunotherapeutic role of PD-L1 inhibitors in HCC, which can help in exploring new therapeutic strategies.
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