Extracellular vesicles in lung cancer-From bench to bedside.

Lung cancer is the leading cause of cancer-related deaths worldwide. Despite significant advances in lung cancer research and novel therapies, a better understanding of the disease is crucially needed to facilitate early detection and appropriate diagnoses and to improve treatment outcomes. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are released from all tested cell types and modulate cell-cell communication.

Malignant extracellular vesicles carrying MMP1 mRNA facilitate peritoneal dissemination in ovarian cancer.

Advanced ovarian cancers are highly metastatic due to frequent peritoneal dissemination, resulting in dismal prognosis. Here we report the functions of cancer-derived extracellular vesicles (EVs), which are emerging as important mediators of tumour metastasis. The EVs from highly metastatic cells strongly induce metastatic behaviour in moderately metastatic tumours.

Extracellular vesicles as trans-genomic agents: Emerging roles in disease and evolution.

The composition of genetic material in extracellular vesicles (EV) has sparked interest particularly in the potential for horizontal gene transfer by EV. Although the RNA content of EV has been studied extensively, few reports have examined the DNA content of EV. It is still unclear how DNA is packaged inside EV, and whether they are functional in recipient cells.

Circulating microRNAs and extracellular vesicles as potential cancer biomarkers: a systematic review.

Circulating non-coding RNAs, including microRNAs and long non-coding RNAs, and the protein components of extracellular vesicles are promising biomarkers for the non-invasive detection of cancer at an early stage. This systematic review discusses the increasing number of well-designed cancer biomarker-related studies that have been published worldwide. In many of these studies, high diagnostic accuracy, which is represented as the area under the receiver operating characteristic curve being >0.

The role of extracellular vesicle microRNAs in cancer biology.

microRNAs (miRNAs) constitute a large family of small, approximately 20-22 nucleotide non-coding RNAs that regulate the expression of target genes, mainly at the post-transcriptional level. Multiple studies report that miRNAs are involved in homeostatic maintenance and that aberrant expression of miRNAs is often observed in various types of diseases, including cancer. In cancer biology, miRNAs exert functional roles in tumor initiation, drug resistance, and metastasis.

Chronic treatment of non-small-cell lung cancer cells with gefitinib leads to an epigenetic loss of epithelial properties associated with reductions in microRNA-155 and -200c.

Background: The EGFR tyrosine kinase inhibitor gefitinib is used in therapy for non-small-cell lung cancer (NSCLC). However, its application is limited by resistance-accelerated disease progression, which is accompanied by the epithelial-to-mesenchymal transition (EMT). In the present study, we performed multiple expression analyses of microRNAs (miRNAs) and quantified the expression of several related EMT players in gefitinib-resistant NSCLC cells.

Mesenchymal stem cell-derived extracellular vesicles: a glimmer of hope in treating Alzheimer's disease.

One of the pathological hallmarks of Alzheimer's disease (AD) is the presence of extracellular plaques resulting from the accumulation of beta-amyloid peptide (Aβ). To date, a definitive cure for this disease is still lacking as the currently approved drugs used are mainly symptomatic treatments. The revolutionary discovery of extracellular vesicles (EVs) has shed new light on the development of disease-modifying treatments for AD, owing to their potential in delivering the therapeutic agents to the brain.

Disruption of Circulating Extracellular Vesicles as a Novel Therapeutic Strategy against Cancer Metastasis.

Metastasis is the main cause of cancer mortality for many types of cancer; however, difficulties remain in effectively preventing metastasis. It has been recently and widely reported that cancer-derived extracellular vesicles (EVs) contribute to cancer metastasis. Thus, therapeutic strategies targeting cancer-derived EVs hold great promise because of the possibility of EVs driving the cancer microenvironment toward metastasis.

miR-125b and miR-100 Are Predictive Biomarkers of Response to Induction Chemotherapy in Osteosarcoma.

Osteosarcoma is the most common primary malignancy in bone. Patients who respond poorly to induction chemotherapy are at higher risk of adverse prognosis. The molecular basis for such poor prognosis remains unclear.

Transplantation of Thy1 Cells Accelerates Liver Regeneration by Enhancing the Growth of Small Hepatocyte-Like Progenitor Cells via IL17RB Signaling.

Small hepatocyte-like progenitor cells (SHPCs) transiently form clusters in rat livers treated with retrorsine (Ret)/70% partial hepatectomy (PH). When Thy1 cells isolated from d-galactosamine-treated rat livers were transplanted into the livers of Ret/PH-treated rats, the mass of the recipient liver transiently increased during the first 30 days after transplantation, suggesting that liver regeneration was enhanced. Here we addressed how Thy1 cell transplantation stimulates liver regeneration.

Soluble IL-33 receptor sST2 inhibits colorectal cancer malignant growth by modifying the tumour microenvironment.

Interleukin-33 (IL-33) was recently shown to be involved in the inflammatory tumour microenvironment and the progression of colorectal cancer (CRC). We report here that the expression level of sST2, a soluble form of the IL-33 receptor (ST2L), is inversely associated with the malignant growth of CRC. sST2 is downregulated in high-metastatic cells compared with low-metastatic human and mouse CRC cells.

In vitro reconstitution of breast cancer heterogeneity with multipotent cancer stem cells using small molecules.

A small fraction of tumor cells are thought to possess the potential for both multiple-lineage differentiation and self-renewal, which underlies the cancer stem cell hypothesis. However, the differentiation mechanisms of these cells have not been elucidated due to a lack of appropriate culture methods. Here, we established a culture condition for maintaining multipotent tumor cells from rat breast tumors using 4 small molecules.

Conversion of Terminally Committed Hepatocytes to Culturable Bipotent Progenitor Cells with Regenerative Capacity.

A challenge for advancing approaches to liver regeneration is loss of functional differentiation capacity when hepatocyte progenitors are maintained in culture. Recent lineage-tracing studies have shown that mature hepatocytes (MHs) convert to an immature state during chronic liver injury, and we investigated whether this conversion could be recapitulated in vitro and whether such converted cells could represent a source of expandable hepatocytes. We report that a cocktail of small molecules, Y-27632, A-83-01, and CHIR99021, can convert rat and mouse MHs in vitro into proliferative bipotent cells, which we term chemically induced liver progenitors (CLiPs).

Extracellular Vesicles in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is characterized by the progression of irreversible airflow limitation and is a leading cause of morbidity and mortality worldwide. Although several crucial mechanisms of COPD pathogenesis have been studied, the precise mechanism remains unknown. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are released from almost all cell types and are recognized as novel cell-cell communication tools.

[Investigation into the identities of circulating exosomes].

Exosomes are membrane vesicles approximately 100 nm in diameter, present in a wide range of body fluids, including blood, cerebrospinal fluid, urine and saliva. Exosomes reflect the physiological state of their cells of origin and cancer cell-derived exosomes carry pathogenic components, such as proteins, messenger RNA (mRNA), microRNA (miRNA), and DNA. Thus, exosomes in body fluids provide a rich source of potential biomarkers.

Serum extracellular vesicular miR-21-5p is a predictor of the prognosis in idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis. Although the median survival is 3 years, the clinical course varies to a large extent among IPF patients. To date, there has been no definitive prognostic marker.

How cancer cells dictate their microenvironment: present roles of extracellular vesicles.

Intercellular communication plays an important role in cancer initiation and progression through secretory molecules, including growth factors and cytokines. Recent advances have revealed that small membrane vesicles, termed extracellular vesicles (EVs), served as a regulatory agent in the intercellular communication of cancer. EVs enable the transfer of functional molecules, including proteins, mRNA and microRNAs (miRNAs), into recipient cells.

Concomitant Evaluation of a Panel of Exosome Proteins and MiRs for Qualification of Cultured Human Corneal Endothelial Cells.

Purpose: We elucidate a method to use secreted miRNA profiles to qualify cultured human corneal endothelial cells (cHCECs) adaptable for cell-injection therapy.

Methods: The variations of cHCECs in their composites of heterogeneous subpopulations (SPs) were verified in relation to their surface cluster-of-differentiation (CD) markers. Integrated analysis of micro RNA (miRNA) profiles in culture supernatants (CS) were investigated by 3D-Gene Human microRNA Chips.

Generation of a novel transgenic rat model for tracing extracellular vesicles in body fluids.

Extracellular vesicles (EVs) play an important role in the transfer of biomolecules between cells. To elucidate the intercellular transfer fate of EVs in vivo, we generated a new transgenic (Tg) rat model using green fluorescent protein (GFP)-tagged human CD63. CD63 protein is highly enriched on EV membranes via trafficking into late endosomes and is often used as an EV marker.

Expression Level of Urinary MicroRNA-146a-5p Is Increased in Patients With Bladder Cancer and Decreased in Those After Transurethral Resection.

Background: Bladder cancer is the most prevalent malignancy involving the urinary system and exhibits a markedly high recurrence rate. Therefore, reliable and noninvasive diagnostic and surveillance methods are desperately needed.

Patients And Methods: Candidate microRNAs (miRNAs) were selected from the miRNAs that were differentially expressed in bladder cancer cell lines (T24 and RT4) compared to normal ureteral epithelial tissue using miRNA-microarray analysis.

Global, cancer-specific microRNA cluster hypomethylation was functionally associated with the development of non-B non-C hepatocellular carcinoma.

Background: While hepatitis B and C viral infection have been suppressed, non-B non-C hepatocellular carcinoma (NBNC-HCC) is considered to be rising in incidence terms in some developed countries where prevalence of those viral infections among HCC patients had been very high (such as Japan, Korea, and Italy). To elucidate critical molecular changes in NBNC-HCC, we integrated three large datasets relating to comprehensive array-based analysis of genome-wide DNA methylation (N = 43 pairs) and mRNA/miRNA expression (N = 15, and 24 pairs, respectively) via statistical modeling.

Results: Hierarchical clustering of DNA methylation in miRNA coding regions clearly distinguished NBNC-HCC tissue samples from relevant background tissues, revealing a remarkable tumor-specific hypomethylation cluster.

Efficacy of adjuvant chemotherapy for non-small cell lung cancer assessed by metastatic potential associated with ACTN4.

Although several clinical trials have demonstrated the benefits of platinum-combined adjuvant chemotherapy for resected non-small cell lung cancer (NSCLC), predictive biomarkers for the efficacy of such therapy have not yet been identified. Selection of patients with high metastatic ability in the early stage of non-small cell lung cancer (NSCLC) has the potential to predict clinical benefit of adjuvant chemotherapy (ADJ).In order to develop a predictive biomarker for efficacy of ADJ, we reanalyzed patient data using a public database enrolled by JBR.

How electromagnetic fields can influence adult stem cells: positive and negative impacts.

The electromagnetic field (EMF) has a great impact on our body. It has been successfully used in physiotherapy for the treatment of bone disorders and osteoarthritis, as well as for cartilage regeneration or pain reduction. Recently, EMFs have also been applied in in vitro experiments on cell/stem cell cultures.