The DLC-1 tumor suppressor is involved in regulating immunomodulation of human mesenchymal stromal /stem cells through interacting with the Notch1 protein.

Background: Immunomodulatory activities of human mesenchymal stromal /stem cells (hMSCs) has been widely recognized as the most critical function of hMSCs for exerting its therapeutic effects. However, the detailed mechanisms responsible for regulating the immunomodulation of hMSCs still remain largely unknown. Previous studies revealed that the Notch1 protein exerted a pro-immunomodulatory function probably through interacting with the protein(s) subjective to proteasome-mediated protein degradation.

Human lung epithelial BEAS-2B cells exhibit characteristics of mesenchymal stem cells.

BEAS-2B was originally established as an immortalized but non-tumorigenic epithelial cell line from human bronchial epithelium. Because of general recognition for its bronchial epithelial origin, the BEAS-2B cell line has been widely used as an in vitro cell model in a large variety of studies associated with respiratory diseases including lung carcinogenesis. However, very few studies have discussed non-epithelial features of BEAS-2B cells, especially the features associated with mesenchymal stem cells (MSCs), which represent a group of fibroblast-like cells with limited self-renewal and differentiation potential to various cell lineages.

DLC-1 tumor suppressor regulates CD105 expression on human non-small cell lung carcinoma cells through inhibiting TGF-β1 signaling.

Acquisition of features of mesenchymal cells represents a key step of metastatic progression of cancer cells and searching for mechanisms underlying the acquisition will help design novel clinical strategies for suppressing the metastatic progression. The Deleted in Liver Cancer-1 (DLC-1) gene is a p122/RhoGAP tumor/metastatic suppressor gene. However, the mechanism underlying DLC-1's inhibition of metastasis still remains largely unknown.

Human epithelial ovarian cancer cells expressing CD105, CD44 and CD106 surface markers exhibit increased invasive capacity and drug resistance.

The high rate of mortality associated with ovarian cancer (OC) is due in part to the development of resistance to chemotherapy, which allows the resistant tumour cells to invade and metastasise. Clarifying the mechanistic basis for drug resistance may reveal novel avenues for treatment. The present study investigated the mechanism of paclitaxel (PTX) resistance in human epithelial OC by evaluating the expression of stem cell-associated cell surface markers endoglin (CD105), CD44 antigen and vascular cell adhesion molecule 1 (CD106), in association with the malignant potential of the human OC OVCAR3 cell line and its PTX-resistant derivative OC3/TAX300.

Report of the international conference on manufacturing and testing of pluripotent stem cells.

Sessions included an overview of past cell therapy (CT) conferences sponsored by the International Alliance for Biological Standardization (IABS). The sessions highlighted challenges in the field of human pluripotent stem cells (hPSCs) and also addressed specific points on manufacturing, bioanalytics and comparability, tumorigenicity testing, storage, and shipping. Panel discussions complemented the presentations.

Report of the International Stem Cell Banking Initiative Workshop Activity: Current Hurdles and Progress in Seed-Stock Banking of Human Pluripotent Stem Cells.

This article summarizes the recent activity of the International Stem Cell Banking Initiative (ISCBI) held at the California Institute for Regenerative Medicine (CIRM) in California (June 26, 2016) and the Korean National Institutes for Health in Korea (October 19-20, 2016). Through the workshops, ISCBI is endeavoring to support a new paradigm for human medicine using pluripotent stem cells (hPSC) for cell therapies. Priority considerations for ISCBI include ensuring the safety and efficacy of a final cell therapy product and quality assured source materials, such as stem cells and primary donor cells.

The hUC-MSCs cell line CCRC-1 represents a novel, safe and high-yielding HDCs for the production of human viral vaccines.

MRC-5 represents the most frequent human diploid cells (HDCs)-type cell substrate in the production of human viral vaccines. However, early-passage MRC-5 is diminishing and, due to both technical and ethical issues, it is extremely difficult to derive novel HDCs from fetal lung tissues, which are the common sources of HDCs. Our previous studies suggested that human umbilical cord may represent an alternative but convenient source of new HDCs.

RIG-I and IL-6 are negative-feedback regulators of STING induced by double-stranded DNA.

The stimulator of interferon genes (STING) protein has emerged as a critical signal transduction molecule in the innate immune response. Sustained activation of the STING signaling induced by cytosolic DNA has been considered to be the cause of a variety of autoimmune diseases characterized by uncontrolled inflammation. Therefore, it is important to understand the molecular basis of the regulation of STING signaling pathway.

The notch signaling regulates CD105 expression, osteogenic differentiation and immunomodulation of human umbilical cord mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are a group of multipotent cells with key properties of multi-lineage differentiation, expressing a set of relatively specific surface markers and unique immunomodulatory functions. IDO1, a catabolic enzyme of tryptophan, represents a critical molecule mediating immunomodulatory functions of MSCs. However, the signaling pathways involved in regulating these key properties still remain elusive.

Establishing a Quality Control System for Stem Cell-Based Medicinal Products in China.

Stem cell-based medicinal products (SCMPs) are emerging as novel therapeutic products. The success of its development depends on the existence of an effective quality control system, which is constituted by quality control technologies, standards, reference materials, guidelines, and the associated management system in accordance with regulatory requirements along product lifespan. However, a worldwide, effective quality control system specific for SCMPs is still far from established partially due to the limited understanding of stem cell sciences and lack of quality control technologies for accurately assessing the safety and biological effectiveness of SCMPs before clinical use.

Human diploid MRC-5 cells exhibit several critical properties of human umbilical cord-derived mesenchymal stem cells.

MRC-5 is the most common human diploid cell line used in production of viral vaccines; mesenchymal stem cells (MSCs) is a type of adult multipotent stem cells. Both cell types share the same fibroblast-like morphology and maintain a normal diploid karyotype over long in vitro expansion. However, other than these similarities, very little is known about MRC-5 in terms of biological properties possessed by MSCs.

The regulatory sciences for stem cell-based medicinal products.

Over the past few years, several new achievements have been made from stem cell studies, many of which have moved up from preclinical stages to early, or from early to middle or late, stages thanks to relatively safe profile and preliminary evidence of effectiveness. Moreover, some stem cell-based products have been approved for marketing by different national regulatory authorities. However, many critical issues associated mainly with incomplete understanding of stem cell biology and the relevant risk factors, and lack of effective regulations still exist and need to be urgently addressed, especially in countries where establishment of appropriate regulatory system just commenced.

TRAIL and proteasome inhibitors combination induces a robust apoptosis in human malignant pleural mesothelioma cells through Mcl-1 and Akt protein cleavages.

Background: Malignant pleural mesothelioma (MPM) is an aggressive malignancy closely associated with asbestos exposure and extremely resistant to current treatments. It exhibits a steady increase in incidence, thus necessitating an urgent development of effective new treatments.

Methods: Proteasome inhibitors (PIs) and TNFα-Related Apoptosis Inducing Ligand (TRAIL), have emerged as promising new anti-MPM agents.

The changes of Th17 cells and the related cytokines in the progression of human colorectal cancers.

Background: The role of Th17 cells in colorectal tumorigenesis and development still remains unclear, despite the fact that it has been established in the pathogenesis of autoimmune diseases.

Methods: We first analyzed Th17 cells and Treg cells using flow cytometry in the circulation of colorectal adenoma (CRA) and colorectal carcinoma (CRC) patients and healthy controls, and the frequency of Th17 cells in peripheral blood mononuclear cells (PBMCs) stimulated by anti-CD3 plus anti-CD28 and treated by IL-1β, IL-6, and TGF-β in different concentrations. We then detected cytokines IL-1β, IL-6, IL-17A, IL-21, IL-23 or TGF-β by ELISA in sera and supernatants from both normal and tumor tissues cultured ex vivo.

Comparison of two high-throughput assays for quantification of adenovirus type 5 neutralizing antibodies in a population of donors in China.

Background: The presence of various levels of Adenovirus serotype 5 neutralizing antibodies (Ad5NAb) is thought to contribute to the inconsistent clinical results obtained from vaccination and gene therapy studies. Currently, two platforms based on high-throughput technology are available for Ad5NAb quantification, chemiluminescence- and fluorescence-based assays. The aim of this study was to compare the results of two assays in the seroepidemiology of Ad5NAb in a local population of donors.

[Research advances on Th17 cells in tumor].

The Th17 cells, identified recently as a novel CD4⁺ T cell lineage, are characteristic of their production of IL-17 and distinct from Th1 and Th2 lineages. Their involvement in autoimmune and chronic inflammation diseases has been well observed. Recent evidence suggests that Th17 cells are also involved in tumor immunology.

Proteasome Inhibitor MG132 Induces Apoptosis and Inhibits Invasion of Human Malignant Pleural Mesothelioma Cells.

Malignant pleural mesothelioma (MPM) is an aggressive malignancy tightly associated with asbestos exposure. The increasing incidence of MPM and its resistance to all therapeutic modalities necessitate an urgent development of new treatments for MPM. Proteasome inhibitors (PIs) have emerged as promising agents for treating human cancers that are refractory to current chemotherapies.

DLC-1:a Rho GTPase-activating protein and tumour suppressor.

The deleted in liver cancer 1 (DLC-1) gene encodes a GTPase activating protein that acts as a negative regulator of the Rho family of small GTPases. Rho proteins transduce signals that influence cell morphology and physiology, and their aberrant up-regulation is a key factor in the neoplastic process, including metastasis. Since its discovery, compelling evidence has accumulated that demonstrates a role for DLC-1 as a bona fide tumour suppressor gene in different types of human cancer.

Morphological changes and nuclear translocation of DLC1 tumor suppressor protein precede apoptosis in human non-small cell lung carcinoma cells.

We have previously shown that reactivation of DLC1, a RhoGAP containing tumor suppressor gene, inhibits tumorigenicity of human non-small cell lung carcinoma cells (NSCLC). After transfection of NSCLC cells with wild type (WT) DLC1, changes in cell morphology were observed. To determine whether such changes have functional implications, we generated several DLC1 mutants and examined their effects on cell morphology, proliferation, migration and apoptosis in a DLC1 deficient NSCLC cell line.

The Human mineral dust-induced gene, mdig, is a cell growth regulating gene associated with lung cancer.

Environmental or occupational exposure to mineral dusts, mainly silica and asbestos, is associated with an increased incidence of lung inflammation, fibrosis, and/or cancer. To better understand the molecular events associated with these pulmonary diseases, we attempted to identify genes that are regulated by mineral dusts. Using a differential display reverse transcription polymerase chain reaction technique and mRNAs of alveolar macrophages from both normal individuals and coal miners, we identified a novel mineral dust-induced gene named mdig, which had not been fully characterized.

DLC-1, a Rho GTPase-activating protein with tumor suppressor function, is essential for embryonic development.

DLC-1 (deleted in liver cancer 1) is a Rho GTPase-activating protein that is able to inhibit cell growth and suppress tumorigenesis. We have used homologous recombination to inactivate the mouse DLC-1 gene (Arhgap7). Mice heterozygous for the targeted allele were phenotypically normal, but homozygous mutant embryos did not survive beyond 10.

Aberrant gene expression in human non small cell lung carcinoma cells exposed to demethylating agent 5-aza-2'-deoxycytidine.

The identification of genes undergoing genetic or epigenetic alterations and contributing to the development of cancer is critical to our understanding of the molecular mechanisms of carcinogenesis. A new approach in identifying alterations of genes that might be relevant to the process of tumor development was used in this study by examining the gene expression profile in human lung cancer cells exposed to 5-aza-2'-deoxycytidine (5-aza-dC). A cDNA array analysis was carried out on 5-aza-dC-treated and untreated non small cell lung cancer (NSCLC) cell line NCI-H522.

Expression profile of eukaryotic translation factors in human cancer tissues and cell lines.

Several studies have demonstrated the overexpression of certain eukaryotic translation factors in human cancer cell lines and in malignant tissues. In this study, with human cancer cell lines derived from lungs, breast, prostate, and skin, we have examined the expression profile of 36 translation factors consisting of 27 initiation factors, 8 elongation factors, and 1 termination factor. Translation initiation factors 2C2 and 4E1 and translation elongation factors 1A2 and 1delta were found overexpressed (2- to 2000-fold) in many of the cancer cell lines compared to their corresponding normal cell lines.

CHK2 kinase expression is down-regulated due to promoter methylation in non-small cell lung cancer.

Background: CHK2 kinase is a tumor suppressor that plays important role in DNA damage signaling, cell cycle regulation and DNA damage induced apoptosis. CHK2 kinase expression was known to be ubiquitous in mammalian cells. CHK2-/- cells were remarkably resistant to DNA damage induced apoptosis, mimicking the clinical behavior of non-small cell lung cancer to conventional chemo and radiation therapy.

DLC-1 operates as a tumor suppressor gene in human non-small cell lung carcinomas.

The deleted in liver cancer (DLC-1) gene at chromosome 8p21-22 is altered mainly by genomic deletion or aberrant promoter methylation in a large number of human cancers such as breast, liver, colon and prostate and is known to have an inhibitory effect on breast and liver tumor cell growth. Given the high frequency of deletion involving region 8p21-22 in human non-small cell lung carcinoma (NSCLC), we examined alterations of DLC-1 in a series of primary tumors and tumor cell lines and tested effects of DLC-1 on tumor cell growth. A significant decrease or absence of the DLC-1 mRNA expression was found in 95% of primary NSCLC (20/21) and 58% of NSCLC cell lines (11/19).