Glycosylation changes of vWF in circulating extracellular vesicles to predict depression.

The clinical diagnosis of major depressive disorder (MDD) still depends on subjective information in terms of various symptoms regarding mood. Detecting the characterization of extracellular vesicles (EVs) in blood may result in finding a diagnostic biomarker that reflects the depressive stage of patients with MDD. Here, we report the results on the glycosylation pattern of enriched plasma EVs from patients with MDD.

Herpud1 modulates hypertrophic signals independently of calmodulin nuclear translocation in rat myocardium-derived H9C2 cells.

In this study, we aimed to analyze the role of the Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 (Herpud1) gene in the development of cardiomyocyte hypertrophy in association with Calmodulin (CaM) nuclear translocation and cytosolic Ca levels. To observe the mobilization of CaM in cardiomyocytes, we stably expressed eGFP-CaM in rat myocardium-derived H9C2 cells. These cells were then treated with Angiotensin II (Ang II), which stimulates a cardiac hypertrophic response, or dantrolene (DAN), which blocks the release of intracellular Ca.

Dantrolene reduces platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell proliferation and neointimal formation following vascular injury in mice.

Dantrolene is a ryanodine receptor blocker that is used clinically for treatment of malignant hyperthermia. This study was conducted using murine aortic vascular smooth muscle cells (MOVAS) and a mouse arterial injury model to investigate the inhibitory effect of dantrolene on smooth muscle cell proliferation and migration. We investigated whether dantrolene suppressed platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell proliferation and migration in vitro.

Herpud1 suppress angiotensin II induced hypertrophy in cardiomyocytes.

Purpose: The purpose of this study was to analyze the role of homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 (Herpud1) gene in the development of cardiomyocyte hypertrophy.

Method: In order to examine the effect of suppressing Herpud1 expression, Herpud1 small interfering RNA (siRNA) was introduced into H9C2 cells, which are cell lines derived from rat myocardium, and the degree of Herpud1 protein expression and cell hypertrophy in the Herpud1 siRNA-transfected group and the control group was compared by immunostaining 48 h after Herrpud1 siRNA introduction. To examine whether hypertrophy induced by angiotensin II (Ang II) can be suppressed by the overexpression of Herpud1, the green fluorescent protein (GFP)-Herpud1 plasmid was introduced into H9C2 cells, and the degree of cell hypertrophy was examined in the GFP-Herpud1-and control groups for 48 h.

4-Phenylbutyrate restores localization and membrane repair to human dysferlin mutations.

Dysferlinopathies are muscular dystrophies caused by recessive loss-of-function mutations in dysferlin (), a membrane protein involved in skeletal muscle membrane repair. We describe a cell-based assay in which human DYSF proteins bearing missense mutations are quantitatively assayed for membrane localization by flow cytometry and identified 64 localization-defective DYSF mutations. Using this platform, we show that the clinically approved drug 4-phenylbutryric acid (4-PBA) partially restores membrane localization to 25 mutations, as well as membrane repair to cultured myotubes expressing 2 different mutations.

Anti-Cancer Role and Therapeutic Potential of Extracellular Vesicles.

Cell-cell communication is an important mechanism in biological processes. Extracellular vesicles (EVs), also referred to as exosomes, microvesicles, and prostasomes, are microvesicles secreted by a variety of cells. EVs are nanometer-scale vesicles composed of a lipid bilayer and contain biological functional molecules, such as microRNAs (miRNAs), mRNAs, and proteins.

Altered biodistribution of deglycosylated extracellular vesicles through enhanced cellular uptake.

Extracellular vesicles (EVs) from cancer are delivered both proximal and distal organs. EVs are highly glycosylated at the surface where EVs interact with cells and therefore has an impact on their properties and biological functions. Aberrant glycosylation in cancer is associated with cancer progression and metastasis.

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.

A novel platform for cancer therapy using extracellular vesicles.

Extracellular vesicles (EVs) are nanometer-sized membranous vesicles and are involved in cell-to-cell communication. EVs contain several types of functional molecules, such as proteins, mRNAs, and microRNAs (miRNAs). Over the past several years, EVs have emerged as potential tools for a drug delivery system (DDS) that can target organs or cells.

Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood-brain barrier.

Brain metastasis is an important cause of mortality in breast cancer patients. A key event during brain metastasis is the migration of cancer cells through blood-brain barrier (BBB). However, the molecular mechanism behind the passage through this natural barrier remains unclear.

Micromanaging of tumor metastasis by extracellular vesicles.

Extracellular vesicles (EVs) are nanometer-sized membranous vesicles that are released by a variety of cell types into the extracellular space. In the past two decades, EVs have emerged as novel mediators of cancer biology. Many reports have demonstrated the contribution of EVs to cancer metastasis.

Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells.

Breast cancer patients often develop metastatic disease years after resection of the primary tumor. The patients are asymptomatic because the disseminated cells appear to become dormant and are undetectable. Because the proliferation of these cells is slowed, dormant cells are often unresponsive to traditional chemotherapies that exploit the rapid cell cycling of most cancer cells.

RPN2-mediated glycosylation of tetraspanin CD63 regulates breast cancer cell malignancy.

Background: The tetraspanin CD63 is a highly N-glycosylated protein that is known to regulate cancer malignancy. However, the contribution of glycosylation of CD63 to cancer malignancy remains unclear. Previously, we reported that ribophorin II (RPN2), which is part of an N-oligosaccharyle transferase complex, is responsible for drug resistance in breast cancer cells.

Dark side of the exosome: the role of the exosome in cancer metastasis and targeting the exosome as a strategy for cancer therapy.

Cell-cell communication is essential for the regulation of various biological phenomena in multicellular organisms, including development and homeostasis. Deregulation of these interactions leads to inappropriate cell-cell communication, resulting in disease development. Cancer cells communicate closely with the cells in their microenvironment, and this communication promotes malignancy via abnormal growth, invasion, drug resistance and metastasis.

Trash or Treasure: extracellular microRNAs and cell-to-cell communication.

Circulating RNAs in human body fluids are promising candidates for diagnostic purposes. However, the biological significance of circulating RNAs remains elusive. Recently, small non-coding RNAs, microRNAs (miRNAs), were isolated from multiple human body fluids, and these "circulating miRNAs" have been implicated as novel disease biomarkers.

Functional analysis of exosomal microRNA in cell-cell communication research.

Circulating microRNAs (miRNAs), also known as secretory miRNAs, are packaged in small membrane vesicles called exosomes. These exosomal miRNAs are secreted from various cell types and incorporated inside the recipient cells. The functions of exosomal miRNAs are poorly understood, but some reports have shown their essential roles in cancer development.

Prediction of pathologic complete response to sequential paclitaxel and 5-fluorouracil/epirubicin/cyclophosphamide therapy using a 70-gene classifier for breast cancers.

Background: Sequential administration of paclitaxel plus combined fluorouracil, epirubicin, and cyclophosphamide (P-FEC) is 1 of the most common neoadjuvant chemotherapies for patients with primary breast cancer and produces pathologic complete response (pCR) rates of 20% to 30%. However, a predictor of pCR to this chemotherapy has yet to be developed. The authors developed such a predictor by using a proprietary DNA microarray for gene expression analysis of breast tumor tissues.

High genomic grade index associated with poor prognosis for lymph node-negative and estrogen receptor-positive breast cancers and with good response to chemotherapy.

Background: The aim of the present study was to investigate the prognostic value of the genomic grade index for lymph node-negative and estrogen receptor (ER)-positive breast cancers of Japanese women treated with adjuvant hormonal therapy alone, as well as the relation between genomic grade index and pathological complete response (CR) to neoadjuvant chemotherapy.

Methods: Genomic grade index was determined by DNA microarray (U133plus2.0; Affymetrix, Santa Clara, Calif) in tumor tissues obtained from lymph node-negative and ER-positive breast cancers (n = 105) treated with adjuvant hormonal therapy alone or in breast tumor biopsy specimens (n = 84, Mammotome) obtained before neoadjuvant chemotherapy (paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphomide) to investigate the prognostic and predictive values of genomic grade index.

Development of 95-gene classifier as a powerful predictor of recurrences in node-negative and ER-positive breast cancer patients.

Our aim was to develop an accurate diagnostic system using gene expression analysis by means of DNA microarray for prognosis of node-negative and estrogen receptor (ER)-positive breast cancer patients in order to identify a subset of patients who can be safely spared adjuvant chemotherapy. A diagnostic system comprising a 95-gene classifier was developed for predicting the prognosis of node-negative and ER-positive breast cancer patients by using already published DNA microarray (gene expression) data (n = 549) as the training set and the DNA microarray data (n = 105) obtained at our institute as the validation set. Performance of the 95-gene classifier was compared with that of conventional prognostic factors as well as of the genomic grade index (GGI) based on the expression of 70 genes.